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Dr. Bowne's research focuses on developing novel treatment strategies for combating lethal pancreatic cancer and other human malignancies.
Most pancreatic cancers are caused by a mutant, oncogenic protein called ras-p21. This protein, but not its normal variant, causes normal human cells to transform into their malignant counterparts.
Using a computer-based molecular modeling approach, we have developed peptides that are derived from parts of ras-p21 that block cell division caused by the mutant ras-p21 protein but have no effect on the normal form of this protein.
Using a similar approach, we have also identified domains of the p53 protein that possess anti-cancer activity that also blocks the proliferation of cancer cells.
Our Laboratory's research efforts are currently centered upon further elucidating the anti-cancer molecular mechanisms unique to these domains and testing them on pancreatic cancers that grow in established animal models of pancreatic cancer.
Dr. Hirshberg applies computer
modeling and simulation techniques to clinical problems
in trauma such as uncontrolled hemorrhage and
resuscitation. Furthermore he is developing and using
system dynamics models.
The main emphasis of
Dr. Kral's research is investigating mechanisms for the
chronic overnutrition syndrome "obesity" with a view to
prevention and treatment. Early-life stress induces epigenetic changes affecting
neuro-behavioral development leading to
maladaptive energy balance. Food insecurity,
common in our inner-city neighborhood with an
exceptionally high prevalence of obesity is a potent
stressor during gestation. Using questionnaires,
anthropometric measurements, and assays of cortisol
and regulatory peptides we are investigating
predictors of gestational weight gain and maternalfetal
health leading to childhood obesity. In collaboration with the Department of Surgery at
Laval University, Quebec City, we demonstrated
beneficial metabolic effects of maternal obesity
surgery on subsequent pregnancy outcomes
including offspring health carried into adolescence
(JCEM, 2009). We are studying epigenetic markers
that might explain the mechanisms of these effects.
Funded by the Canadian Research Council. Diversionary operations for obesity (e.g. Roux-en-Y
Gastric Bypass) expose segments of small bowel
to undigested nutrients which potentiate signals.
Studies of intestinal perfusion with macronutrients
in spontaneously obese non-human primates at
Downstate will identify mechanisms of weight loss
and assess the kinetics of mucosal adaptation. In
collaboration with the Department of Behavioral
Neuroscience and Psychiatry at Johns Hopkins
University. Funded by the NIH.
Vagotomy interrupts the preparatory, cephalic phase of nutrient intake and digestion in all species studied to date. Clinical follow-up studies in Sweden of severely obese patients 25-30 years after gastric restrictive operations with or without vagotomy, demonstrate a mean 5 units of body mass index weight differential in favor of adding vagotomy. Current Sstudies in progress are evaluating completeness of vagotomy and gastro-intestinal appetitive peptide release in these patients. Privately funded.
In a multi-national collaboration with surgeons,
endocrinologists and geneticists in Europe we demonstrated
monogenic changes affecting eating
behavior and metabolism in severely obese candidates
for obesity surgery (NEJM, 2003). With functional
genotyping and 6+ years of clinical follow-up
we are studying the predictive capacity of polymorphisms
affecting outcomes of mechanistically
different operations for severe metabolic obesity.
Vagotomy interrupts the preparatory, cephalic
phase of nutrient intake and digestion in all
species studied to date. Clinical follow-up studies
in Sweden of severely obese patients 25-30 years
after gastric restrictive operations with or without
vagotomy, demonstrate a mean 5 units of body
mass index weight differential in favor of adding clinical relevance as noted above.
The scientific goals
of the research program include:
Determination of the overall contribution of specific
genetic elements to colorectal cancer incidence in
special populations. These genetic elements include
the APC gene, the DNA mismatch repair genes
(MSH2, MLH1, MSH6 and PMS1/2) and the MYH gene.
Clarification of the carrier frequencies in the
general population of pathologic alleles in these
genes associated with CRC incidence.
Identification of novel genetic elements associated
with CRC predisposition through the utilization of
linkage analysis, single nucleotide polymorphism
(SNP) and haplotype analysis and genome wide
association studies (GWAS).
These goals include mentoring young investigators
including surgical residents and fellows in CRC genetics
and genomics research.
Dr. Lee's research includes several
federally funded investigations directed at understanding
the pathogenesis of cardiac disease on a molecular
and whole organ level as well as elements of clinical
outcome associated with cardiac surgery including
factors that impact on other tissue sites. These studies
involve a range of methodologies that span different
spatial and temporal scales and degree of invasiveness.
Active projects:
-
Neurocognitive dysfunction and cerebral perfusion
in cardiac surgery.
Aim: Use functional brain imaging and optical biomarkers
to predict neurological complications of
cardiac surgery.
Funding Source: NINDS/NIH.
Autoimmune response in ischemia-reperfusion.
We are investigating the effects of myocardial
ischemia-reperfusion on autoimmune response and
the complement cascade. This may lead to novel
diagnostic and treatment strategies for myocardial
injury.
Funding Source: NHLBI/NIH
Omega-3 fatty acids for prevention of post-operative
atrial fibrillation.
This is an international, multicenter, randomized
clinical trial. Other participating sites in the United
States include: Emory, Vanderbilt, Brigham and
Women's Hospital, Washington University, and
Brown University.
Funding Sources: GlaxoSmithKlline,
Pronova, Sigma-Tau, and the NIH.
Brain-computer interface and injury recovery.
This is a multi-institutional effort led by SUNY
Downstate Medical Center to study the brain's
plasticity, or ability to recover from injury.
Funding
Source: DARPA/Department of Defense.
Optical tomography to diagnose breast cancer.
We seek to validate metrics for breast cancer
detection from a robotic, dual-sensing, functional
optical imaging system.
Funding Source: New York
State Department of Health, DARPA/Department of
Defense, and NCI/NIH.
Thomas K. Weber, MD, FACS
Dr. Weber's long term strategic research goal is to facilitate and advance the participation of the Downstate Department of Surgery and the Veterans Health Administration in the nation's effort to understand the genetics of predisposition to colorectal cancer. His goals include facilitating patient access to state-of-the-art cancer and genomics research; a benefit directly related to the successes of the Human Genome Project (web) with significant clinical relevance as noted above.
The scientific goals of the research program include:
-
Determination of the overall contribution of specific genetic elements to colorectal cancer incidence in special populations. These genetic elements include the APC gene, the DNA mismatch repair genes (MSH2, MLH1, MSH6 and PMS1/2) and the MYH gene.
-
Clarification of the carrier frequencies in the general population of pathologic alleles in these genes associated with CRC incidence.
Identification of novel genetic elements associated with CRC predisposition through the utilization of linkage analysis, single nucleotide polymorphism (SNP) and haplotype analysis and genome wide association studies (GWAS).
These goals include mentoring young investigators including surgical residents and fellows in CRC genetics and genomics research. |
