ARTIFICIAL BREEDING OF CHIMPANZEES
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Abstract: Work has continued in the past year to improve artificial breeding methods for the chimpanzee. Methods for superovulation have been developed using human menopausal gonadotropins. The success rate of A.I. has been raised to over 80% for a single insemination when specific parameters of the inseminated cycle have been met. At this time such identification is by observation of the spontaneous cycle, however, future work will be directed to iatrogenic initiation of such highly fertile cycles. The alteration in fertility is likely associated with endometrial development and alteration of implantation rate. As a consequence of a restriction in breeding of the common chimpanzee, we are increasing efforts directed to creation and cryobanking of embryos created using In vitro fertilization and ICSI. To date embryos have been banked from the common chimpanzee (P. Troglodytes) and the sooty mangabey (c. Atys). In addition, we are studying the potential effects of fish an tifreeze proteins as cryoprotectants for semen storage
Keywords: aging; clinical research; endocrine gland /system; growth /development; Mammalia; Primates; reproductive system; women`s health
Project start date: 1998-05-01
Project end date: 1999-04-30
Budget start date: 1-OCT-1997
Budget end date: 30-SEP-1998
5P51RR000165-38_0021 (1998): $0
Sponsored Links Excellgen http://Excellgen.com
SUGARS AS NOVEL CRYOPROTECTANTS FOR PRIMATE OOCYTES
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Assisted reproduction, including in vitro fertilization (IVF) is an important part of medical treatment for women who have difficulty conceiving naturally. IVF involves hormonal stimulation of the woman to induce multiple follicle development with surgical recovery of oocytes for fertilization. This procedure may have to be repeated on several occasions. Freeze preservation of female gametes would reduce the stress associated with repeated IVF. While it is practical to freeze preserve embryos, freeze preservation of primate oocytes has not been predictable successful. Embryo storage is not always the best option, for example when oocyte recovery prior to chemotherapy etc. would allow future use of IVF for a woman not associated with a partner at the time of treatment. In addition, certain legal problems associated with embryo freezing could be avoided. Oocyte preservation would also be of value in conservation programs for endangered species. This work tests the use of sugars as cryoprotective agents for primate oocytes in the primate model as there are genetic differences in oocytes which have precluded application of methods developed for storage of (for example) hamster oocytes
Keywords: Biological Preservation; chemotherapy; Computer Retrieval of Information on Scientific Projects Database; Cryoprotective Agents; Development; Embryo; Female; Fertilization; Fertilization in Vitro; Freezing; Funding; Future; Genetic; Germ Cells; Grant; Hamsters; Hormonal; Infertility; Institution; Legal; Medical; Methods; Modeling; novel; Oocytes; Operative Surgical Procedures; Primates; Procedures; programs; Recovery; Reproduction; Research; Research Personnel; Resources; Source; Stress; sugar; Testing; Time; United States National Institutes of Health; Woman; Work
Project start date: 2007-05-01
Project end date: 2008-04-30
Budget start date: 1-MAY-2007
Budget end date: 30-APR-2008
5P51RR000165-47_7553 (2007): $31600
ARTIFICIAL BREEDING OF CHIMPANZEES
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Abstract: This program has been directed to development of assisted breeding techniques for the chimpanzee and other nonhuman primates. Methods for collection and cryostorage of semen have been established and fertility of stored sperm demonstrated. In vitro fertilization of chimpanzee oocytes is routine, there has been no term pregnancy in the chimpanzee after IVF, although we have identified three chemical pregnancies. However, we believe we have identified a potential reason for this situation, which has to do with the characteristics of the menstrual cycle used for reimplantation of the embryos. Thus, we have correlated an increase in Al success with the pattern of the menstrual cycle endocrine changes such that in the optimum cycle, Al success rate is over 80% for a single insemination, as opposed to around 20% for unselected cycles. That change is hypothesized to relate to endometrial development and the success of implantation. As a result of the present moratoriu m on chim panzee breeding, we have cryobanked chimpanzee embryos at the 8 - 16 cell stage for future use rather than immediately using them for reimplantation. FUNDING NIH / RR03587-1151 $207,223 4/01/93 - 8/31/98 PUBLICATIONS Gould, K.G. and Younis, A.I Potential use of fish antifreeze proteins in primate sperm cryopreservation. Cryobiology (In press). Younis, A.I., Rooks, B., Khan, S. and Gould, K.G. The effects of antifreeze peptide III (AFP) in insulin transferrin selenium (ITS) on cryopreservation of chimpanzee (Pan troglodytes) spermatozoa. J. Androl. 19207-214, 1998. P51RR00165-38 1/1/98 - 12/31/98 Yerkes Regional Primate Research Center
Keywords: Mammalia; reproductive system; technology /technique
Project start date: 1999-05-01
Project end date: 2000-04-30
Budget start date: 1-OCT-1998
Budget end date: 30-SEP-1999
5P51RR000165-39_0035 (1999): $0
CHIMPANZEE BREEDING & RESEARCH PROGRAM
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Abstract: This is a pilot study to attempt to immunize male and female macaques to an androgen dependent, epididymis specific protein associated with sperm function. The rationale is that immunization of the female, with secretion of antibody into the female reproductive tract, will interfere with fertilization. The DNA associated with expression of EP2 was used as antigen, administered intradermally using a gene gun. Of eight females injected, two demonstrated evidence of antibody formation. Although possible delayed, pregnancy was not inhibited. Future work will be directed to optimization of the vaccination schedule and alteration of the route of DNA administration in order to maximize antibody production prior to reproductive challenge. FUNDING Yerkes / Venture Funding $20,000 5/01/97 - 4/30/98 PUBLICATIONS PR51RR00165-38 1/1/98 - 12/31/98 Yerkes Regional Primate Research Center
Keywords: clinical research; endocrine gland /system; growth /development; Mammalia; reproductive system; women`s health
Project start date: 1976-06-01
Project end date: 2001-04-30
Budget start date: 1-OCT-1998
Budget end date: 30-SEP-1999
5P51RR000165-40_0037 (2000): $36936
DEVELOPMENT OF DNA VACCINES FOR CONTRACEPTION
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Abstract: This is a pilot study to attempt to immunize male and female macaques to an androgen dependent, epididymis specific protein associated with sperm function. The rationale is that immunization of the female, with secretion of antibody into the female reproductive tract, will interfere with fertilization. The DNA associated with expression of EP2 was used as antigen, administered intradermally using a gene gun. Of eight females injected, two demonstrated evidence of antibody formation. Although possible delayed, pregnancy was not inhibited. Future work will be directed to optimization of the vaccination schedule and alteration of the route of DNA administration in order to maximize antibody production prior to reproductive challenge. FUNDING Yerkes / Venture Funding $20,000 5/01/97 - 4/30/98 PUBLICATIONS PR51RR00165-38 1/1/98 - 12/31/98 Yerkes Regional Primate Research Center
Keywords: clinical research; endocrine gland /system; growth /development; Mammalia; reproductive system; women`s health
Project start date: 1999-05-01
Project end date: 2000-04-30
Budget start date: 1-OCT-1998
Budget end date: 30-SEP-1999
5P51RR000165-39_0037 (1999): $0
5P51RR000165-38_0022 (1998): $0
REPRODUCTIVE PARAMETERS OF CHIMPANZEE MODEL
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Abstract: The work is directed to investigation of the androgen dependent proteins within the chimpanzee epididymis, with the potential for development of contraceptive vaccines. We have identified EP2 as androgen dependent and have identified several different splicing variants of the EP2 gene. The two main variants, EP2A and EP2B, differ in that they are transcribed by different promoters. The N-terminal sequence of both variants possess concensus sequences for a signal peptidase cleavage site, as expected for a secretory protein. Using a genomic clone of EP2, we are int the process of identifying the promoter and any associated androgen-binding sequences. We are currently expressing the EP2 protein in a bacterial system, as antibody generation in rabbits and chickens has been unsatisfactory, to use the expressed protein as antigen. When this antibody is obtained we will continue studies to elucidate the function of EP2 in post-testicular sperm maturation. As a separate part of these studies we have published a detailed report on the immunohistochemical localization of the epididymal secretory protein EP1 in the chimpanzee epididymis
Keywords: aging; clinical research; endocrine gland /system; growth /development; Mammalia; Primates; reproductive system; women`s health
Project start date: 1998-05-01
Project end date: 1999-04-30
Budget start date: 1-OCT-1997
Budget end date: 30-SEP-1998
5P51RR000165-38_0020 (1998): $0
5P51RR000165-39_0034 (1999): $0
5P51RR000165-40_0036 (2000): $36936
CHIMPANZEE BREEDING & RESEARCH PROGRAM
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Abstract: Contraception As virtually all of our animals are housed socially, considerable effort has continued to be invested in contraception to prevent new pregnancies. To continue observation of menstrual cyclicity, we have chosen IUDs as the primary method of contraception. Thus far, with over 508 cycles of breeding exposure, we have observed three pregnancies and only one clinical problem migration of an IUD from the uterus into the bladder). This is a 0.6% failure rate, in keeping with that predicted from human use. The expected life of the IUD is at least 5 years. Placement is monitored by direct visualization, ultrasound, or x-ray at time of routine clinical survey. In addition, several females within the breeding cohort have been implanted with Norplant and 6 males have undergone vas ligation. To date, DNA has been collected from 124 chimpanzees using the Puregene kit. This is an ongoing process that includes genotyping by Dr. Stone and his staff at Trinity Univ ersity as required for colony management. Standard Operating Procedures have been written and implemented for carestaff to assist in enrichment duties at the Main Center. In addition, the Emory Policy on Environmental Enrichment for Nonhuman Primates has been updated to reflect recent elaborations to the program, and an extensive bibliography has been attached for training purposes. In the next year, we intend to maintain strict limits on chimpanzee breeding and to continue to focus on improving the management of our chimpanzee colony. These plans include use of positive reinforcement training vs. unstructured human interaction as enrichment for chimpanzees housed in indoor-outdoor runs; documentation of the course and success of social introductions and introduction of new projects involving joystick-controlled computer video tasks as enrichment. FUNDING NIH / RR03591 $417,694 9/01/95 - 8/31/00 PUBLICATIONS Gould, K.G. Use of IUDs as a management tool for the chimpanzee (Pan troglodytes). J. Med. Primatol. (In press). P51RR00165-38 1/1/98 - 12/31/98 Yerkes Regional Primate Research Center
Keywords: behavioral /social science research tag; Mammalia; psychology; reproductive system
Project start date: 1999-05-01
Project end date: 2000-04-30
Budget start date: 1-OCT-1998
Budget end date: 30-SEP-1999
5P51RR000165-39_0036 (1999): $0
ARTIFICIAL BREEDING OF CHIMPANZEES
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Abstract: A series of related experiments and studies has been conducted to further enhance the breeding of the chimpanzee and to develop methods for the recovery, maturation and preservation of primate gametes. These studies are important for continued preservation of the chimpanzee and other primates; for development of methods for increasing the population of the bonobo; and for application to the human with regard to problems of infertility. The effects of certain agents known to stabilize oocyte cytoskeletal elements were evaluated for freezing of immature and mature rhesus monkey oocytes. These agents, cytochalasin-B and EGTA (ethylene glycol-bis(-aminoethyl ether) N,N,N,N-tetracetic acid, produced a significantly higher (77.6 vs 50%, p<0.01) morphological survival rate than did control media when tested in three replicated experiments. The fertilization rate and development rate of fertilized oocytes were not different between the control and test groups. These results sug gest that use of these stabilizing agents will improve freeze preservation of immature and mature oocytes. A second series of experiments was designed to assess the effects of Antifreeze Protein (AFP) and Insulin-Transferrin-Selenium (ITS) on chimpanzee (Pan troglodyte) spermatozoa during the freeze-thaw process. The AFP or ITS were added to the semen sample at varied concentrations of 0, 1, 10 and 100 mg/ ml. The semen from each animal was processed independently prior to exposure to the AFP or ITS. The fresh semen samples were collected by artificial vagina, analyzed for sperm count, viability, and motility using a computer assisted motion analysis (CAMA). The Curvilinear Velocity, Linearity, and Straight Line Velocity declined somewhat from the original pre-freeze values but remained constant among the different concentrations of ITS. The Lateral Head Movement remained close to the pre-freeze value. A concentration of 100 mg/ml gave no recovery of sperm motility. Best re sults were obtained after addition of 10 mg/ml AFP and 1 mg/ml ITS. These results have significance for the storage of semen at wet ice temperatures for transportation. With respect to collection and maturation of oocytes, preantral follicles have been isolated from four ovaries by two methods; (i) collagenase dissociation 5 mg/ml collagenase enzyme alone was used to dissociate two ovaries. It was possible to collect a clean preparation of up to 150 preantral follicles (with denuded basement membrane of theca cells i.e., oocyte-granulosa cell complex) and 50 or more free cumulus-enclosed oocytes from a single animal. The ages of animals that supplied these follicles were 3 to 18 years. (ii) microdisection, using microdisection we were able to mechanically dissect up to 20 intact preantral follicles from a single animal. This work will be extended in order to isolate a larger number of viable follicles and to devise media which will support their maturation in vitro. Studies on in vitro fertilization have been extended to include the use of oocytes from the pygmy chimpanzee (P. paniscus) and the sooty mangabey (C.atys) in accord with the goa ls of ongoing, funded work. P51RR00165-36 1/1/96 - 12/31/96 Yerkes Regional Primate Research Center
Keywords: aging; endocrine gland /system; growth factor; Mammalia; Primates; reproductive system; women`s health
Project start date: 1997-05-01
Project end date: 1998-04-30
Budget start date: 1-OCT-1996
Budget end date: 30-SEP-1997
5P51RR000165-37_0036 (1997): $0
Sponsored Links Excellgen http://Excellgen.com
PORPHYRINS AS MICROBICIDES FOR STDS
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Keywords: animal colony; Primates
Project start date: 2005-05-01
Project end date: 2006-04-30
Budget start date: 1-MAY-2005
Budget end date: 30-APR-2006
5P51RR000165-45_0136 (2005): $32021
SAFETY STUDY OF ANTI-HUMAN APO-1/FAS MOUSE/HUMAN MONOCLONAL IGM ANTIBODY
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Project start date: 2005-05-01
Project end date: 2006-04-30
Budget start date: 1-MAY-2005
Budget end date: 30-APR-2006
5P51RR000165-45_7306 (2005): $30784
PORPHYRINS AS MICROBICIDES FOR STDS
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Keywords: animal colony; antiinfective agents; biotechnology; biotherapeutic agent; drug design /synthesis /production; microorganism disease chemotherapy; porphyrins; Primates; sexually transmitted diseases
Project start date: 2004-05-01
Project end date: 2005-04-30
Budget start date: 1-MAY-2004
Budget end date: 30-APR-2005
5P51RR000165-44_0136 (2004): $35765
CHIMPANZEE MANAGEMENT RESEARCH PROGRAM
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Project start date: 2003-05-01
Project end date: 2004-04-30
Budget start date: 1-MAY-2003
Budget end date: 30-APR-2004
5P51RR000165-43_6432 (2003): $31173
PORPHYRINS AS MICROBICIDES FOR STDS
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Project start date: 2003-05-01
Project end date: 2004-04-30
Budget start date: 1-MAY-2003
Budget end date: 30-APR-2004
5P51RR000165-43_6507 (2003): $31173
REPRODUCTIVE PARAMETERS OF CHIMPANZEE MODEL
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Keywords: biotechnology; endocrine gland /system; Mammalia; model design /development; reproductive system
Project start date: 2002-05-01
Project end date: 2003-04-30
Budget start date: 1-OCT-1998
Budget end date: 30-SEP-1999
5P51RR000165-42_0034 (2002): $209143
ARTIFICIAL BREEDING OF CHIMPANZEES
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Keywords: Mammalia; reproductive system; technology /technique
Project start date: 2002-05-01
Project end date: 2003-04-30
Budget start date: 1-OCT-1998
Budget end date: 30-SEP-1999
5P51RR000165-42_0035 (2002): $209143
CHIMPANZEE BREEDING & RESEARCH PROGRAM
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Keywords: behavioral /social science research tag; Mammalia; psychology; reproductive system
Project start date: 2002-05-01
Project end date: 2003-04-30
Budget start date: 1-OCT-1998
Budget end date: 30-SEP-1999
5P51RR000165-42_0036 (2002): $209143
DEVELOPMENT OF DNA VACCINES FOR CONTRACEPTION
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Keywords: clinical research; endocrine gland /system; growth /development; Mammalia; reproductive system; women`s health
Project start date: 2002-05-01
Project end date: 2003-04-30
Budget start date: 1-OCT-1998
Budget end date: 30-SEP-1999
5P51RR000165-42_0037 (2002): $209143
Grants awarded to G Kenneth
THE ROLE OF MTDNA MUTATIONS IN BETA-CELL FAILURE
G Kenneth
Saint Louis Universitycity: Saint Louis country: United States (us)
Grant 5F30AG029104-04 from National Institute On Aging
Abstract: Type 2 diabetes, a heterogeneous disorder of polygenic origin, is associated with defects in beta cell function and insulin action. While the nature of the beta cell defect has yet to be determined, chronic oxidative stress resulting from elevated plasma levels of glucose and lipids appears to be an important factor in the loss of beta cell mass during diabetes development. Mitochondrial DNA (mtDNA) is uniquely sensitive to oxidative stress, and increased levels of mtDNA mutations (>20-30%) are associated with diabetes development in patients with mitochondria! disease; however, a much greater impact on the etiology of Type 2 diabetes may arise from the somatic accumulation of random mtDNA mutations (levels 0.01- 0.1 %) that occurs with age in nearly all individuals. The contribution of mutations at these levels to the development of diabetes is unknown. The broad goal of this research is to test the hypothesis that increased levels of random mutations in beta cell mtDNA lead to the loss of beta-cell function and the inability to maintain normal glycemic control. Specific aims are to elucidate the physiological impact of rising levels of mtDNA mutations in beta cells and to confirm that transgene toxicity does not contribute to diabetes development
Keywords: Age; Beta Cell; Biochemical; blood glucose regulation; cell injury; Cell physiology; Cells; Chronic; Defect; design; Development; Diabetes Mellitus; diabetic; Disease; DNA; DNA-Directed DNA Polymerase; Etiology; Failure (biologic function); Genetic; Genome; Glucose; glycemic control; Goals; Individual; insight; Insulin; Lead; Lipids; Mediating; MELAS; Mitochondria; Mitochondrial Diseases; Mitochondrial DNA; mitochondrial DNA mutation; Molecular; Mus; Mutation; Nature; Non-Insulin-Dependent Diabetes Mellitus; Oxidative Stress; Pancreas; Patients; Physiological; Plasma; Prevention; Promotor (Genetics); Rattus; Regulation; Research; Role; Testing; Therapeutic; Toxic effect; Transgenes; Transgenic Organisms
Project start date: 2006-07-01
Project end date: 2010-06-30
Budget start date: 1-JUL-2009
Budget end date: 30-JUN-2010
PFA/PA: PA-05-151
5F30AG029104-04 (2009): $44726
5F30AG029104-03 (2008): $44522
5F30AG029104-02 (2007): $30258
1F30AG029104-01 (2006): $30258
NGVL: GENE THERAPY STUDY IN HIV INDIVIDUALS
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Support for Dr. Zaia in an experimental gene therapy study in HIV-infected individuals
Keywords: Computer Retrieval of Information on Scientific Projects Database; Funding; gene therapy; Grant; Individual; Institution; Research; Research Personnel; Resources; Source; United States National Institutes of Health
Project start date: 2005-09-01
Project end date: 2007-08-31
Budget start date: 1-SEP-2005
Budget end date: 31-AUG-2007
3U42RR011148-10S4_7744 (2007): $56046
NGVL: SAFETY TESTS SERVICES TO NGVL CENTERS GENERATING CLINICAL GRADE MATERIAL
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. PROVIDE SAFETY TESTS PERFORMED UNDER GOOD LABORATORY PRACTICE
Project start date: 2005-09-01
Project end date: 2007-08-31
Budget start date: 1-SEP-2005
Budget end date: 31-AUG-2007
PFA/PA: RFA-RR-01-001
3U42RR011148-10S3_0006 (2006): $368559
NGVL: RETROVIRAL VECTOR PRODUCTION FOR CLINICAL USE
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. CLINCAL GRANT MATERIAL WILL BE GENERATED WHICH MEETS FDA SPECIFICATIONS
Project start date: 2005-09-01
Project end date: 2007-08-31
Budget start date: 1-SEP-2005
Budget end date: 31-AUG-2007
PFA/PA: RFA-RR-01-001
3U42RR011148-10S3_0003 (2006): $368559
NGVL: LENTIVIRAL VECTOR PRODUCTION FOR CLINICAL USE
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. DEVELOP PRODUCTION METHODS FOR CLINICAL GRADE LENTIVIRAL VECTOR
Project start date: 2005-09-01
Project end date: 2007-08-31
Budget start date: 1-SEP-2005
Budget end date: 31-AUG-2007
PFA/PA: RFA-RR-01-001
3U42RR011148-10S3_0004 (2006): $368559
NGVL: PROVIDE SCIENTIFIC & REGULATORY SUPPORT FOR INVRSTIGATORS USING VECTORS
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. ASSIST INVESTIGATORS IN OPTIMIZING VECTOR CONSTRUCTION & PRODUCTION
Project start date: 2005-09-01
Project end date: 2007-08-31
Budget start date: 1-SEP-2005
Budget end date: 31-AUG-2007
PFA/PA: RFA-RR-01-001
3U42RR011148-10S3_0005 (2006): $368559
NATIONAL GENE VECTOR LABORATORY AT INDIANA UNIVERSITY: HEART FAILURE STUDY
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. for the production of the AAV6 vector to be used in the heart failure study proposed by Dr. Barry London
Project start date: 2005-09-01
Project end date: 2006-08-31
Budget start date: 1-SEP-2005
Budget end date: 31-AUG-2006
PFA/PA: RFA-RR-01-001
3U42RR011148-10S1_0001 (2006): $442875
Sponsored Links Excellgen http://Excellgen.com
NATIONAL GENE VECTOR LABORATORY AT INDIANA UNIVERSITY
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. not available
Project start date: 2005-09-01
Project end date: 2007-08-31
Budget start date: 1-SEP-2005
Budget end date: 31-AUG-2007
PFA/PA: RFA-RR-01-001
3U42RR011148-10S2_0002 (2006): $1265524
NGVL: ADMINISTRATE THE NGVL COORDINATING CENTER
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Abstract: This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. COORDINATE MEETINGS OF NGVL REVIEW AND STEERING COMMITTEE
Project start date: 2005-09-01
Project end date: 2007-08-31
Budget start date: 1-SEP-2005
Budget end date: 31-AUG-2007
PFA/PA: RFA-RR-01-001
3U42RR011148-10S3_0007 (2006): $368559
COMPREHENSIVE MINORITY AND HEALTH DISPARITIES RESEARCH CENTER
G Kenneth, Professor Of Medicine
University Of Alabama At Birminghamcity: Birmingham country: United States (us)
Grant 3P60MD000502-08S1 from National Center On Minority Health And Health Disparities
Abstract: This revision proposes to establish a Center of Excellence in Comparative Effectiveness Research for Eliminating Disparities (CERED) to 1) conduct research on the comparative effectiveness of health care delivery strategies within health disparities (HD) populations; 2) conduct comparative effectiveness research (CER) on the impact of different treatments in the reduction of HD, including the development of innovative research methods for evaluating effectiveness in HD populations; 3) establish effective dissemination strategies to ensure that HD populations and the health care providers and systems that serve them are aware of and capable of utilizing the results of CER; 4) promote linkages to patient data registries and networks that can partner with our UAB CERED in HD-relevant CER and dissemination; and 5) promote participation of HD populations in CER studies. The CERED will be established in partnership between two University-wide Interdisciplinary Research Centers with a long history of collaboration the Minority Health and Health Disparities Research Center and the Center for Outcomes Effectiveness Research and Education. The overall goal is to enhance the capacity of the parent P60 to conduct CER as related to HD by expanding the current infrastructure to include CER, training, and dissemination. The specific aims are to 1) Implement a subproject, "Cost Effectiveness of Interpreter Services A Randomized Controlled Trial," comparing the effectiveness of health services delivered in cultural and linguistic context; 2) Support CER through funding of developmental pilot projects; 3) Create an HD CER mentored training and career development track within the HDRTP infrastructure provided through the parent grant; 4) Promote linkages to patient data registries and networks that enroll minority patients; and 5) Develop, utilize, and promote effective models for disseminating CER findings and promoting their translation into interventions, programs, and policies for HD populations and providers. The supplement will expand the scope of all three cores of the parent grant (Research, Research Training, and Community Engagement) by adding a CER focus to each in order to accomplish the parent grant´s goal of reducing and ultimately eliminating health disparities
Keywords: ARHGEF5 gene; career development; Collaborations; Communities; comparative effectiveness; compare effectiveness; cost effectiveness; Data; Development; Educational aspects; Effectiveness; effectiveness research; Enrollment; Ensure; Funding; Goals; health care delivery; health disparity; Health Personnel; Health Services; innovation; Interdisciplinary Study; intervention program; Linguistics; Mentors; Minority; minority health; Modeling; Outcome; parent grant; Parents; Patients; Pilot Projects; Policies; Population; population health; Provider; Randomized Controlled Trials; Recording of previous events; Registries; Research; Research Infrastructure; Research Methodology; research study; Research Training; Services; System; Training; Translations; trial comparing; Universities
Project start date: 2010-09-18
Project end date: 2012-04-30
Budget start date: 18-SEP-2010
Budget end date: 30-APR-2012
PFA/PA: RFA-MD-10-500
3P60MD000502-08S1 (2010): $1400000
AUTOMATED NUCLEIC ACID EXTRACTOR SYSTEM:AUTOGENFLEX STAR/AUTOGEN QUICK-GENE 810
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Grant 1S10RR027710-01 from National Center For Research Resources
Abstract: This request is for funds to purchase a nucleic acid extraction system consisting of an AutoGenFlex Star automated DNA isolation system and the AutoGen Quick-Gene 810 RNA isolation unit. The instruments will be housed, managed, and maintained by the Indiana Clinical and Translational Sciences Institute (CTSI) within the IndianaCTSI Specimen Storage Facility. Biobanking has become an integral part of translational research. The rapid developments in high throughput sequencing along with novel bioinformatic analytical tools has led to an increase in the number of investigators performing novel genetic analysis. With this increase in analytical capacity, the limiting step has become the collection and isolation of nucleic acids. The equipment will facilitate health research for the CTSI member institutions Indiana University (IU), Purdue University and the University of Notre Dame. All three members of the Indiana CTSI will share a common state-of-the-art repository that was built, in part, through a NCRR construction grant (C06-RR020128-01, 09/30/04 - 09/29/08, R.S. Fife, PI, K. Cornetta, Co-I). The facility will be housed at the IU School of Medicine. In addition to supporting individual investigators, the IU Simon Cancer Center (2P30CA082709), the National Cell Repository for Alzheimer Disease (5U24AG021886; PI T. Foroud), the National Gene Vector Biorepository (P40 RR024928; PI K. Cornetta), and the Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center work closely with the Indiana CTSI repository efforts. As a result, the instrument system will have an impact on a much larger group of NIH funded investigators than those located in Indiana. The facility will serve as a recharge center for users and the service contract and reagent costs will be included in user fees. The CTSI will provide support for a technician dedicated to repository activities including DNA processing and equipment maintenance. By developing a common facility, the Indiana CTSI will facilitate sample collection and processing, promote sharing of samples, and assure compliance with international biobanking standards. The equipment requested in this proposal will improve consistency of biospecimens, increase capacity, and free up technician time for analytical work. Furthermore, the diverse group of investigators who will utilize this equipment will ensure the investment will facilitate basic and clinical research in almost every area of medicine. Understanding the genetic basis of disease continues to foster the development of new treatments for both common and rare diseases. Automated extraction of DNA can facilitates genetic analysis, a benefit that will positively affect almost every area of clinical medicine and the capacity to provide RNA will allow Indiana investigators to pursue this rapidly expanding field. The equipment requested will improve the research for R01 funded investigators, national biobanking efforts, and Indiana CTSI investigators engaged in basic and clinical research
Keywords: Affect; Alzheimer`s Disease; analytical tool; Area; Arts; base; biobank; Bioinformatics; Cancer Center; Cells; Clinical; Clinical Medicine; Clinical Research; Collection; Contract Services; cost; Development; Disease; DNA; Ensure; Equipment; Fees; Fostering; Funding; Genes; Genetic; genetic analysis; Grant; Health; Housing; improved; Indiana; Individual; Institutes; Institution; instrument; International; Investments; Maintenance; medical schools; Medicine; member; National Center for Research Resources; novel; Nucleic Acids; Process; Rare Diseases; Reagent; repository; Research; Research Personnel; RNA; sample collection; Sampling; Specimen; System; Time; Tissue Banking; Tissue Banks; Translational Research; United States National Institutes of Health; Universities; vector; Work
Project start date: 2010-02-20
Project end date: 2011-02-19
Budget start date: 20-FEB-2010
Budget end date: 19-FEB-2011
PFA/PA: PAR-09-028
1S10RR027710-01 (2010): $159460
IN VIVO EVALUATION OF CANDIDATE DRUGS
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Abstract: This project is directed to establishing the toxicity and pharmacodynamics, in the mouse, of drugs developed in the proposed program by studying the clinical effects of extended vaginal and intraperitoneal administration at doses equal to and in excess of those predicted to be clinically effective. Pharmacodynamics, here defined as organ location and rate of tissue accumulation of the test drug(s) in the rodent model will be determined in collaboration with investigators in projects 2.4. Tissue location and accumulation will be demonstrated by HPLC and capillary electrophoretic analyses of tissue samples as described in Project l, and by use of in vivo tests developed in Project 2. In addition we will evaluate the potential effects of candidate drugs on male fertility as determined by the effects of in vitro exposure of agents to primate sperm on sperm viability, morphology and in vitro measures of fertilizing capacity. A final aim of this project is to determine the efficacy of vaginal instillation of candidate drugs on SIV infection in non-human primates inoculated with SIV by the vaginal route. The proposed research will utilize metallonatural porphyrins (MNPs) developed and tested in vitro in the other projects and will provide initial evidence of toxicity in an in vivo model. Further, it will provide preliminary evidence of clinical efficacy of MNPs against viral infection in a primate model
Keywords: antiAIDS agent; capillary electrophoresis; drug adverse effect; drug screening /evaluation; fertility; hamsters; high performance liquid chromatography; injection /infusion; laboratory mouse; Macaca nemestrina; Pan; pharmacokinetics; porphyrins; sexually transmitted diseases; simian immunodeficiency virus; sperm; topical drug application
Project start date: 2000-09-01
Project end date: 2001-08-31
5P01AI045883-02_0005 (2000): $68784
1P01AI045883-01_0005 (1999): $0
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Abstract: The Vector Cores is designed to facilitate gene therapy research and was established during the first funding period. This shared facility has allowed consolidated of resources and promoted interactions among thje gene therapy investigators at IU. During the initial funding period, the Vector Core sought to facilitate basic retroviral gene therapy research by supplying certified packaging of cell lines and supernate. The components of the Vector Core are (1) A production laboratory capable of generating retroviral vectors using certified packaging cell lines. Funds are requested to support generation of packaging cell lines for basic science efforts of the CCEMH, including production of retroviral and lentiviral material. CCEMH funds are not requested to support the clinical production efforts of the Vector Core; (2) a Vector Testing Laboratory which can assay packaging cell lines or other material used by CCEMH investigators to insure they are pathogen free; and (3) a Molecular Diagnostic Laboratory which provides CCEMH investigators to insure they are pathogen free; and (3) a Molecular Diagnostic Laboratory which provides CCEMH investigators with rapid vector determinations and estimation of gene transfer using quantitative PCR. In addition, the laboratory is skilled at assessing gene transfer into hematopoietic progenitors using PCR of individual progenitor colonies. The Molecular Diagnostic Laboratory is also involved with sample processing for clinical gene therapy samples. For the upcoming funding period, the core will (1) provide investigators with high titer retroviral and lentiviral packaging cell lines, (2) provide molecular diagnostic services, including quantitative PCR, and (3) provide consistent handling of clinical samples from patients participating in gene therapy trials and provide safety testing of clinical samples as mandated by the FDA
Keywords: biological products; biomedical facility; cell line; hematology; human tissue; polymerase chain reaction; Retroviridae; transfection /expression vector
Project start date: 2002-09-01
Project end date: 2003-08-31
Budget start date: 1-OCT-1998
Budget end date: 30-SEP-1999
5P30DK049218-09_9002 (2002): $228564
3P30DK049218-07S1_9002 (2001): $228564
5P30DK049218-08_9002 (2001): $228564
5P30DK049218-07_9002 (2000): $120834
Sponsored Links Excellgen http://Excellgen.com
2P30DK049218-06_9002 (1999): $0
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Abstract: The Vector Core is designed to facilitate gene therapy research and has been an active part of this PPG throughout its funding. It has met and exceeded the specific aims during prior funding periods. This shared facility has allowed consolidation of resources and promoted interactions among the gene therapy investigators at IU. While the Core initially provided support for retroviral gene transfer, it has been heavily invovled with the development of lentiviral vectors for PPG investigators. The core will continue to provide PPG investigators with the following services (1) Access to plasmid, cell lines, and other reagents used in the generation of gene transfer vectors, (2) Generation and characterization of retroviral and lentiviral vectors for preclinical work, (3) Molecular Diagnostics Services, and (4) Access to BL3 Facilities and assistance with regulatory requirements. The objectives include new services such as LAM-PCR and production of foamy viral vectors
Keywords: Cell Line; Clinical; Clinical Trials; design; Development; Diagnostic Services; Funding; gene replacement therapy; gene therapy; Gene Transfer; gene transfer vector; Generations; Hematopoietic stem cells; Lentivirus Vector; meetings; Molecular; Plasmids; pre-clinical; Production; Reagent; Research Personnel; Resources; Retroviral Vector; Services; Therapeutic Studies; vector; Viral Vector; Work
Budget start date: 1-JUL-2009
Budget end date: 30-JUN-2010
5P01HL053586-15_9002 (2009): $164160
5P01HL053586-14_9002 (2008): $156667
NATIONAL GENE VECTOR LABORATORY AT INDIANA UNIVERSITY
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Grant 3U42RR011148-10S1 from National Center For Research Resources
Abstract: The purpose of this grant application is to allow IU to continue as a NGVL production center. The investigators wish to provide service to the gene therapy community by producing and distributing clinical grade vectors for Phase I/II gene transfer protocols. They also propose to continue as the NGVL Coordinating Center. The aims of this application include generate and certify retroviral vectors intended for clinical use; generate and certify lentiviral vectors intended for clinical use; and provide scientific and regulatory support for investigators using vectors generated in the NGVL. They will facilitate clinical investigators in preparing their clinically-based Investigational New Drug Application (IND), allowing cross-reference to the IU Vector Production Drug Master File. They will provide relevant safety tests services to other NGVL centers generating clinical grade material. The IU vector production facility has an extensive experience in the certification of vectors and offers a variety of safety tests performed under Good Laboratory Practice. They will make these assays available to other NGVL centers who might otherwise need to outsource this work. Finally, they will administer the NGVL Coordinating Center. The Coordinating Center will coordinate the meetings of the NGVL Review Committee and Steering Committee, process investigator requests for NGVL services, oversee compliance with investigators responsibilities as described in the NGVL Policy and Procedures Manual, maintain the NGVL Toxicology Master File(s), and collect post-distribution monitoring data from all NGVL-funded investigators
Project start date: 1995-08-01
Project end date: 2009-08-31
Budget start date: 1-SEP-2005
Budget end date: 31-AUG-2009
PFA/PA: RFA-RR-01-001
3U42RR011148-10S1 (2006): $442875
3U42RR011148-10S2 (2006): $1265524
3U42RR011148-10S3 (2006): $1842795
5U42RR011148-10 (2005): $1609334
5U42RR011148-09 (2004): $1259004
5U42RR011148-08 (2003): $1251902
5U42RR011148-07 (2002): $1694989
Sponsored Links Excellgen http://Excellgen.com
NATIONAL GENE VECTOR LABORATORY
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Grant 2U42RR011148-06 from National Center For Research Resources
Abstract: The purpose of this grant application is to allow IU to continue as a NGVL production center. The investigators wish to provide service to the gene therapy community by producing and distributing clinical grade vectors for Phase I/II gene transfer protocols. They also propose to continue as the NGVL Coordinating Center. The aims of this application include generate and certify retroviral vectors intended for clinical use; generate and certify lentiviral vectors intended for clinical use; and provide scientific and regulatory support for investigators using vectors generated in the NGVL. They will facilitate clinical investigators in preparing their clinically-based Investigational New Drug Application (IND), allowing cross-reference to the IU Vector Production Drug Master File. They will provide relevant safety tests services to other NGVL centers generating clinical grade material. The IU vector production facility has an extensive experience in the certification of vectors and offers a variety of safety tests performed under Good Laboratory Practice. They will make these assays available to other NGVL centers who might otherwise need to outsource this work. Finally, they will administer the NGVL Coordinating Center. The Coordinating Center will coordinate the meetings of the NGVL Review Committee and Steering Committee, process investigator requests for NGVL services, oversee compliance with investigators responsibilities as described in the NGVL Policy and Procedures Manual, maintain the NGVL Toxicology Master File(s), and collect post-distribution monitoring data from all NGVL-funded investigators
Keywords: biomedical facility; cooperative study; gene delivery system; Lentivirus; microorganism culture; transfection /expression vector
Project start date: 1995-08-01
Project end date: 2006-08-31
Budget start date: 30-SEP-2001
Budget end date: 31-AUG-2002
PFA/PA: RFA-RR-01-001
2U42RR011148-06 (2001): $1049938
NATIONAL GENE VECTOR LABORATORY AT INDIANA UNIVERSITY
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Grant 3U42RR011148-10S4 from National Institute Of Allergy And Infectious Diseases
Abstract: The purpose of this grant application is to allow Indiana University to continue as a National Gene Vector Laboratory (NGVL) Production Center. We wish to provide service to the gene ¿´mtherapy*community.jby;?producing anddistributing clinical grade-vectors;for-Phase I and n gene transfer protocols. We also propose to continue as the NGVL Coordinating Center. The Aims of this application include (1) Generate and certify retroviral vectors intended for clinical use. (2) Generate and certify lentiviral vectors intended for clinical use. (3) Provide scientific and regulatory support for investigators using vectors generated in the NGVL. We will facilitate clinical investigators in preparing their clinically-based Investigation^ New Drug Application (IND), allowing cross-reference to the Indiana University Vector Production Drug Master File. (4) Provide relevant safety tests services to other NGVL centers generating clinical grade material. The Indiana University Vector Production Facility has an extensive experience in the certification of vectors and offers a variety of safety tests performed under Good Laboratory Practice. We will make these assays available to other NGVL centers who might otherwise need to outsource this work. (5) To administrate the NGVL Coordinating Center. The Coordinating center will coordinate the meetings of the NGVL Review Committee and Steering Committee, process investigator requests for NGVL services, oversee compliance with-investigatorsresponsibilities as described in the NGVL Policy and Procedures Manual, maintain the NGVL Toxicology Master File(s), and collect post-distribution monitoring data from all NGVL funded investigators
Project start date: 1995-08-01
Project end date: 2009-08-31
Budget start date: 1-SEP-2005
Budget end date: 31-AUG-2009
PFA/PA: RFA-RR-01-001
3U42RR011148-10S4 (2007): $56046
SURFACE DEPENDENT REACTIONS IN THROMBOSIS AND THROMBOLYSIS
G Kenneth, Professor
University Of Vermont & St Agric Collegecity: Burlington country: United States (us)
Grant 5P01HL046703-20 from National Heart, Lung, And Blood Institute
Abstract: The overall focus of this program is aimed at identifying the components of, and the mechanisms for, the processes which maintain the balance between the fluidity and clotting of blood. The components associated with the maintenance of blood fluidity include elements of the plasma, the circulating blood cells, the vascular tissues and their surrounding tissues. The processes responsible for maintaining or altering the fluidity of blood include the coagulation reactions, the pro and anticoagulant functions associated with peripheral blood and vascular cells and the vascular-blood fibrinolytic system. The projects in this Program address, in an integrated fashion, the global reactions associated with each of these processes and their regulation. The fundamental hypothesis is that the properties of the complex multifaceted systems contributing to hemostasis and fibrinolysis are embodied in, and can be deduced from detailed knowledge of the structure, interactions and reactions of the individual components of the systems. The studies focus both upon systems reconstructed from purified components and on natural biomaterials and biosystems, including mechanistic and population studies of thrombophilia. Our strategy is to combine our talents dealing with the molecular and physiological interactions occurring on these biological surfaces and to correlate this knowledge with human health and disease. The program is composed of four projects 1) The Activation of Prothrombin, 2) Venous Thromboembolism Genes, Risk and Management, 3) Properties of Fibrinolytic Cascade, 4) Regulation of Human Platelet Prothrombinase Activity. An Administrative Core and an Immunology Core support these projects. Overall, these projects and cores are integrated with respect to their purpose and the reagents which they share (natural and recombinant proteins, nucleic acids, synthetic inhibitors, peptide substrates, antibodies and cells) in chemical cellular and epidemiological studies aimed at understanding the processes of human thrombosis and hemostasis. The research proposed extends from fundamental studies of molecular genetics, cell biology and biochemistry to the genetics and mechanisms of the pathology of human thrombotic disease and bleeding disorders. The proposed research program and the historical evidence of past research accomplishments demonstrate that significant interactions, both intellectual and physical, exist between the principal investigators and the laboratories which make this program project grant an effective scientific vehicle
Relevance: Relevance: It is estimated that half the population of the USA and Europe will die of diseases that involve a blood clot. Depending upon the organ affected, the disease will be called a heart attack, stroke or pulmonary embolism but the underlying cause is a clot in a blood vessel. The research in this program aims to develop sufficient knowledge to predict risk and suggest interventional procedures to block blood clots
Project start date: 1997-09-01
Project end date: 2012-07-31
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
5P01HL046703-20 (2011): $1873190
G Kenneth, Professor
University Of Vermont & St Agric Collegecity: Burlington country: United States (us)
Abstract: The goal of this project is to characterizethe physiology and pathology of the blood coagulation system in quantifiable terms. We have developed three approaches for these analyseswhich include numerical models of the blood coagulation proteome, numerical recapitulations of the blood coagulation proteome using purified proteins, and studies of whole blood in vitro and flowing from microvascular wounds. We seek quantitatively transparent descriptions convergent with the biological/pathologic observations of medicine which can ultimately be useful for the diagnosis, prophylaxis and therapy of human thrombotic and lemorrhagic disease. In the renewal requested, we will evaluate, in the closed blood coagulation systems, the influence of additional components of the plasma proteome on the generation of thrombin and other constituents. Special emphasis will be focused on tissue factor from natural sources, protein S, and cellular contributions by platelets, monocytes and endothelial cells. We will apply our methods to open systems, initially using flow dynamics in two artificial systems, to investigate the binding and presentation of the components of the proteolytic coagulation complexes under conditions of shear ranging from venous to arterial. These experiments will be conducted using total internal reflectance fluorescence and a newly devised tool the Real Time Thrombosis Profiler. Experiments in flow will be quantitatively analyzed using biophysical techniques and evaluated using modern mathematical techniques used to describe flow dynamics. Flow reactions will be studied in systems ranging from artificial capillaries coated with synthetic . membrane films or endothelial cells, and ultimately to human vascular arterial and venous segments. The systems developed will be utilized to evaluate the influence of anticoagulants and antiplatelet agents on the coagulation response. We anticipate the latter studies will provide evidence for identifying control points and the qualities of new agents required for control of these points. Project 1 is integrated with each of the remaining five projects of this program project grant providing both intellectual material and physical support in the collaborative studies of coagulation and fibrinolysis in human biology. Relevance Venous and arterial blood clots are major health problems in the United States associated with approximately one million deaths each year. Hemorrhagic diseases, especially hemophilia A and B are thankfully less frequent, but still major health issues for those affected. This project seeks to provide fundamental knowledge which will be useful to identify those at risk for thrombotic and bleeding diseases, and provide methods and information that can be useful in the diagnosis, prophylaxis and therapy of bleeding and clotting diseases. ^^
Keywords: Affect; Anticoagulants; Antiplatelet Drugs; Binding (Molecular Function); Biochemical; Biological; Blood capillaries; Blood Cells; Blood Circulation; Blood Clot; Blood coagulation; blood coagulation process; Blood Platelets; Blood Vessels; capillary; Cessation of life; Coagulation Process; Complex; Development; Diagnosis; Disease; Endothelial Cells; Endothelium; Fibrinolysis; Film; Fluorescence; Generations; Goals; Health; Hemophilia A; Hemophilia B; Hemorrhage; Human; Human Biology; In Vitro; Intervention; Knowledge; Medicine; Membrane; Methods; Modeling; monocyte; New Agents; Pathologic; Pathology; Physiology; Plasma; Program Research Project Grants; Prophylactic treatment; Protein S; Proteins; Proteome; Prothrombin; Reaction; research study; response; Risk; Source; Surface; System; Techniques; Testing; Thrombin; thrombolysis; Thromboplastin; Thrombosis; Time; tool; United States; Venous; Whole Blood
Budget start date: 1-AUG-2011
Budget end date: 31-JUL-2012
5P01HL046703-20_0001 (2011): $323655
ARTIFICIAL BREEDING OF ANIMALS
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Abstract: The goal is to further establish artificial breeding of chimpanzees as an effective means for increasing the birth rate at facilities in the United States which house populations of these animals. Three specific objectives form the basis for the specific aims of the project. First, the effectiveness of artificial insemination methodology will be improved by evaluation of the type of hormone treatment used to induce and synchronize ovulation time. The optimum route for semen delivery, and the minimum semen quality and optimum concentration will be determined. Second, improved methods for cryopreservation of semen from chimpanzees will be evaluated and monitored using in vitro tests designed to identify maintained fertilizing capacity and morphological integrity. Third, a semen bank will be established primarily for chimpanzee semen, with addition of other ape semen when available. This artificial breeding program should 1) be inexpensive to maintain, 2) provide additional knowledge concerning the reproductive physiology of the great apes, and 3) be adaptable to zoos desiring to improve their own colonies of these animals. Just as important will be the maintained integrity of these animals through maximum use of the gene pool. It is essential to provide a continued and adequate supply of great apes, particularly chimpanzees, for biomedical research in to human health-related problems for which they are the only applicable models, and this research is a sensible and necessary adjunct to development of a National Breeding and Research Program
Keywords: animal colony; animal population genetics; artificial fertilization; hamsters; Pan; radioimmunoassay; scanning electron microscopy; veterinary science
Project start date: 1986-09-30
Project end date: 1989-09-29
Budget start date: 30-SEP-1988
Budget end date: 29-SEP-1989
PFA/PA: RFA-RR-86--01
5R24RR003587-03 (1988): $0
5R24RR003587-02 (1987): $0
NEW FACULTY RECRUITMENT TO THE INDIANA UNIVERSITY GENE THERAPY PROGRAM
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Grant 5P30HL101337-02 from National Heart, Lung, And Blood Institute
Abstract: The Gene and Cell Therapy Program (GCTP) at Indiana University is a highly interactive group of investigators with a 15-year history of multi-departmental interaction and collaborative research. The program has a focus on the genetic manipulation of stem cells and is home to a world-class facility for the manufacture of clinical gene therapy products (funded by a NCRR construction grant). Indiana University is the NHLBI designated site for clinical lentiviral vector production through its Gene Therapy Resources Program. Indiana University is also the site of the National Gene Vector Biorepository funded by the NCRR/NIH. A NHLBI funded Program Project Grant (PI Dinauer) has facilitated the collaborations in the GCTP. Moreover, a NHLBI funded training grant in gene therapy has trained 5 pre-doctoral students and 22 post-doctoral fellows. An NIDDK training grant in hematopoiesis has trained 22 pre-doctoral students and 26 post-doctoral fellows. This P30 application will enhance this interactive group of gene and cell therapy experts while providing a proven, productive environment for the development of junior faculty. Specific Aim The aim of this proposal is to fund recruitment of a junior faculty with expertise in gene transfer that can facilitate clinical trial and develop novel production methodology. The individual we seek to move to a tenure track position is Scott Witting, Ph.D. This P30 grant will enhance the Gene and Cell Therapy Program at Indiana University. Dr. Scott Witting will be hired as an Assistant Professor tenure track and develop an independent research program aimed at identifying the optimal, clinically relevant, gene transfer methodology for transduction of hematopoieitic and other stem cell products. This will facilitate clinical trials proposed by the GCTP members
Keywords: biobank; Cancer Grant Supplements (P30); Cell Therapy; Clinical; clinical research site; Clinical Trials; clinically relevant; Collaborations; Development; Doctor of Philosophy; Environment; Faculty; Funding; gene therapy; Gene Transfer; Genes; genetic manipulation; Grant; Hematopoiesis; Home environment; Indiana; Individual; Lentivirus Vector; manufacturing facility; member; Methodology; National Center for Research Resources; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; novel; Positioning Attribute; Postdoctoral Fellow; pre-doctoral; Production; professor; Program Research Project Grants; programs; ranpirnase; Recording of previous events; Research; Research Personnel; Resources; Site; Stem cells; Students; Training; Universities; vector
Relevance: This P30 grant will enhance the Gene and Cell Therapy Program at Indiana University. Dr. Scott Witting will be hired as an Assistant Professor tenure track and develop an independent research program aimed at identifying the optimal, clinically relevant, gene transfer methodology for transduction of hematopoieitic and other stem cell products. This will faciliate clinical trials proposed by the GCTP members
Project start date: 2009-09-30
Project end date: 2011-08-31
Budget start date: 1-SEP-2010
Budget end date: 31-AUG-2011
PFA/PA: RFA-OD-09-005
5P30HL101337-02 (2010): $289172
1P30HL101337-01 (2009): $407810
CLINICAL APPLICATIONS OF MODULATION OF DNA REPAIR PATHWAYS
G Kenneth, Joe C. Christian Professor & Chairman
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Abstract: The clinical studies outlined in this specific aim target the manipulation of 06-methylguanine DNA methyltransferase (MGMT) in humans and are the result of extensive pre-clinical work demonstrating the efficacy of the approaches in animal models. One project proposes to increase the expression of MGMT in hematopoietic cells in an effort to diminish the cumulative myelosuppression commonly encountered with chloroethylnitrosoureas (CENUs). This project utilizes a recombinant retroviral vector extensively tested in murine studies and produced by the National Gene Vector Laboratory at Indiana University for human clinical trials. The clinical study builds on a current pilot study at Indiana University, designed by Dr. Regina Jakacki and supported in part by NCI funding, which utilities peripheral blood stem-progenitor cell infusions to decrease hematopoietic toxicities and allow schedule compression of an extensively used brain treatment protocol called "PCV" (procarbazine, CCNU, vincristine). The second project is designed to diminish expression of MGMT in tumor cells. Based on pre-clinical work by Dr. Leonard Erickson, MGMT can be effectively depleted from tumor cell lines by the sequential treatment with agents that produce the natural substrate for MGMT, 06-methylguanine, or act as a substrate for MGMT directly. One such agent, 06-benzylguanine (6-BG), is currently in phase I trials at other institutions. The specific aims of the study are 1) To conduct a pilot study of dose-intensified procarbazine, CCNU, vincristine (PCV) for poor prognosis pediatric and adult brain tumor utilizing fibronectin-assisted, retroviral-mediated modification of CD34+ peripheral blood cells with 06-methylguanine DNA methyltransferase (MGMT). 2) To conduct a phase I trial to determine the toxicity of the combination of 06-benzylguanine and BCNU, and to examine the inhibition of MGMT activity in tumor biopsies in patients treated with this combination chemotherapy for relapsed B cell malignancies
Keywords: antineoplastics; biopsy; brain neoplasms; carmustine; CD34 molecule; clinical research; clinical trial phase I; combination cancer therapy; cytotoxicity; DNA repair; drug screening /evaluation; enzyme activity; enzyme inhibitors; genetic manipulation; human subject; human therapy evaluation; lomustine; methyltransferase; neoplasm /cancer chemotherapy; neoplasm /cancer genetics; neoplastic cell; pharmacokinetics; procarbazine; streptozotocin; vincristine
Project start date: 2002-03-01
Project end date: 2003-02-28
Budget start date: 1-OCT-1997
Budget end date: 30-SEP-1998
5P01CA075426-05_0004 (2002): $220099
5P01CA075426-04_0004 (2001): $220099
Sponsored Links Excellgen http://Excellgen.com
5P01CA075426-03_0004 (2000): $248024
5P01CA075426-02_0004 (1999): $0
1P01CA075426-01A1_0004 (1998): $0
G Kenneth
Emory Universitycity: Atlanta country: United States (us)
Abstract: The chimpanzee is a primate species closely related to the human. The species has been shown to be of great use in the study of endocrine, physiologic, medical and cognitive factors. Previous research has been directed to the investigation and improvement of artificial breeding methods for the chimpanzee. That work was undertaken in order to supplement the chimpanzee breeding program, thus ensuring the continued availability and viability of the captive population and eliminating the need for further removal of animals from the wild. The proposed work will continue to develop previous work related to artificial breeding and realization of the potential genetic diversity within the existing captive population; will extend the use of the existing captive chimpanzee population in conservation of other endangered species e.g. (P.paniscus) and will extend our use of IVF techniques in other nonhuman primates for investigation of the mechanism of transfer of immunity to SIV and HIV; and will conduct studies which will provide information relevant to future use of the chimpanzee in study of health related problems directly related to women, e.g., subfertility and premenstrual syndrome (PMS). Specifically, we propose to 1. Improve identification and control of the ´normal´ endocrine changes associated with the menstrual cycle of the chimpanzee with particular reference to the role of prolactin and oxytocin in modification of luteal function; 2. Develop methods for the initiation and maintenance of interspecific/intergeneric pregnancy both in monkeys and great apes; 3. Investigate novel methods for the storage of primate spermatozoa at low, but above freezing, temperatures; and 4. Maintain a germ plasm cryobank, with increased use of oocyte storage to further develop the concept of the frozen ark for nonhuman primate species
Keywords: animal breeding; animal colony; artificial immunosuppression; Cercocebus; chorionic gonadotropin; cryopreservation; egg /ovum; embryo /fetus preservation; embryo /fetus transplantation; female reproductive system disorder diagnosis; hamsters; in vitro fertilization; laboratory mouse; Macaca mulatta; menstrual cycle disorder; ovulation detection /prediction; oxytocin; Pan; pregnancy; pregnancy disorder chemotherapy; prolactin; sperm; tissue /organ preservation; xenotransplantation
Project start date: 1986-09-30
Project end date: 1998-08-31
Budget start date: 1-APR-1997
Budget end date: 31-AUG-1998
3R01RR003587-11S1 (1998): $0
5R01RR003587-09 (1995): $0
5R01RR003587-08 (1994): $0
2R01RR003587-07A1 (1993): $0
AMERICAN SOCIETY OF GENE THERAPY ANNUAL MEETING (2009-2013)
G Kenneth, Joe C. Christian Professor & Chairman
American Society Of Gene Therapycity: Milwaukee country: United States (us)
Grant 1R13HL097543-01 from National Heart, Lung, And Blood Institute
Abstract: The American Society of Gene Therapy was founded in 1996 and is dedicated to the development of gene and cell therapies with a particular focus on professional and public education. Our Annual Meeting represents the major educational initiative of the Society and has been CME accredited for all of our prior 11 meetings. This R13 proposal requests support for travel grants and an educational program for trainees. Over 1/4 of our members are scientists in training working to develop clinically applicable gene-based technologies. Trainee participation in the Annual Meeting is fostered by an outstanding educational program, trainee travel awards, and recognition of outstanding scientific accomplishments through peer-reviewed trainee Excellence in Research Awards. Over the past decade, the ASGT has offered 470 travel grants and 63 Research Awards, with 20 travel grants per year for the past 5 years made possible by an R13 grant from the NHLBI. Educational opportunities for travel awardees include outstanding plenary speakers, state-of-the-art scientific symposia, and educational sessions that review current thinking on a variety of topics. In addition to leading scientists and clinicians, the program includes ethicists and representatives from the FDA, OBA, and NIH so young scientists may gain insight into the compliance and ethical issues related to human gene therapy. Trainees are active presenters in oral and poster presentations and the top trainee s are recognized at the Presidential Symposium. This proposal also requests partial support of a novel "Meet the Expert" program that allows trainees to interact with gene therapy leaders in a small group setting. The size of the ASGT meeting (approximately 2,000 participants) is ideally suited to expose young scientists to leaders in the field, yet provide opportunities for trainees to present their work at the premier meeting in the field of gene and cell therapy. Continued NIH support for the ASGT Annual Meeting will allow continued educational and professional advancement of trainees in the field of cell and gene therapy. (End of )
Keywords: ing; American; Arts; Award; base; Cell Therapy; Cells; Development; Educational Grants; Ethical Issues; Ethicists; Fostering; Funding; gene therapy; Genes; Grant; Human; innovation; insight; meetings; member; National Heart, Lung, and Blood Institute; novel; Oral; Participant; Peer Review; Postdoctoral Fellow; posters; programs; public education; Request for Proposals; Research; Research Personnel; Scientific Advances and Accomplishments; Scientist; Senior Scientist; Societies; Students; symposium; Technology; Thinking, function; Training; Travel; United States National Institutes of Health; Work
Relevance: The American Society of Gene Therapy (ASGT) is seeking funding for 30 travel awards for post- doctoral fellows and students for each year of the project. In addition, ASGT is seeking funding to support each year for the innovative "Meet-the-Investigator" sessions which enable post- doctoral fellows and students in the field to interact with high profile, senior scientists in the field of gene and cell therapy
Project start date: 2010-05-01
Project end date: 2011-04-30
Budget start date: 1-MAY-2010
Budget end date: 30-APR-2011
PFA/PA: PA-08-149
1R13HL097543-01 (2010): $10000
IMPROVED STORAGE OF SEMEN AT LOW TEMPERATURE
G Kenneth
City: country:
Abstract: SPID# 37 In order to develop improved methods for semen preservation which do not require sophisticated technology and which will permit collection of semen samples from the wild if needed, we are presently assessing the effects of Antifreeze Protein (AFP) and Insulin- Transferrin-Selenium (ITS) on chimpanzee (Pan troglodytes) spermatozoa during an abbreviated freeze-thaw process. The AFP or ITS are added to the diluent of the semen sample at concentrations of 0, 1, 10 and 100 mg/ ml. The semen from each animal was processed independently prior to exposure to the AFP or ITS. The fresh semen samples were collected by artificial vagina, analyzed for sperm count, viability, and motility using computer assisted motion analysis (CAMA). CAMA was performed on these samples to determine the post-thaw motility characteristics. Semen was frozen at wet ice temperature (approx 0 deg C.) for up to 96 hours. The motility of sperm in the fresh semen sample of the AFP experimental group was 66.0 %. The addition of AFP in varied concentrations of 1,10, and 100 mg/ml resulted in a decline in themotility but a constancy in all four motility parameters. The 100 mg/ml treatment gave a 96% post-thaw sperm motility which was similar to that of the fresh sample. The other two concentrations resulted in a dramatic decline with approximately a 10% recovery of sperm motility. The motility of sperm in the fresh semen sample of the ITS experimental group was 88.5%. Cryopreservation accompanied with addition of ITS in concentrations of 1, 10, and 100 mg/ml resulted in a decline in motility as well as a decline in three of the four motility parameters. The Curvilinear Velocity, Linearity, and Straight Line Velocity declined from the original pre-freeze value but remained constant among the different concentrations of ITS. The Lateral Head Movement remained close to the pre-freeze value. A concentration of 100 mg/ml ITS gave no recovery of sperm motility. Best results were obtained after addition of 100 mg/ml AFP
Keywords: cryopreservation; cryoprotective agents; method development; Pan; semen; sperm; sperm motility; tissue /organ preservation
2P51RR000165-36_0037 (1996): $0
ENDOMETRIAL PROTEIN EXPRESSION AS ASSOCIATED WITH EMBRYO IMPLANTATION RATE
G Kenneth
City: country:
Abstract: SPID# 36 While the endocrine and physiological parameters of the human menstrual cycle are well documented, precise details of the ´fertile´ (as identified by established pregnancy) as opposed to the ´nonfertile´ cycle, are not well defined. In addition, there is a recognized incidence of ´idiopathicinfertility´ which exists even when male factors have been eliminated. Such rnormals though rinfertiles cycles also appear to occur in female common chimpanzees (Pan troglodytes), and have been identified by detailed monitoring of estrogen and progesterone fluctuations. It is hypothesized that the infertility is due to altered protein expression by the endometrium at time of implantation; this alteration appears to follow on from a distinctive pattern of estrogen secretion during the follicular phase. A matched series of serum samples and endometrial biopsies were collected from the two types of cycle using a sensitive external marker of follicular activity (the Perineal Swelling pattern) to distinguish the two types of cycle and schedule the sampling. Serum samples were obtained between six and nine days after menses either before or after a critical change in the marker; this change has been demonstrated to occur immediately prior to a doubling of estrogen concentrations. Endometrial biopsies were collected during the luteal phase five days after the peri-ovulatory peak in luteinizing hormone (LH) and three or four days after a distinctive and associated alteration in the external marker. These biopsies are being processed to identify the relative expression of various integrins (attachment proteins), particularly (V(3, which has been shown to vary in expression during the luteal phase. Histological sections are subject to quantitative fluorescence microscopy. After quantitation of the protein expression, we will verify the predicted fertility status of the cycle by use of artificial insemination, a technique which can now achieve greater than 80% pregnancy after a single insemination
Keywords: biopsy; embryo implantation; endometrium; estrogens; fertility; fluorescence microscopy; gene expression; histology; hormone regulation /control mechanism; Pan
2P51RR000165-36_0036 (1996): $0
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