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Biography and Eduation:
Dr. David Gortler is an FDA subject matter expert in the
areas of atherosclerosis, atheroprogression, cholesterol metabolism (including:
statin pharmacology and lipid/ LDL/ HDL modulation) and obesity. Dr. Gortler is
proficient in the drug development process, the drug approval process, clinical
trial design, the FDA efficacy/safety review process and drug labeling.
Among
other reviews, Dr. Gortler was the lead FDA clinical reviewer for the SEARCH
Trial: (Study of the Effectiveness of Additional Reductions in Cholesterol and
Homocysteine) which compared simvastatin 20mg to 80mg. Prior to being a Senior
Medical Analyst and Medical Officer at the FDA in the Office of New Drugs, Dr.
Gortler was an Assistant Professor of Pharmacology at Yale University, and prior
to that he was an early-phase Investigational Medicine Scientist at Pfizer Inc
in the area of lipid metabolism and atherosclerosis. Dr. Gortler helped initiate
Pfizer’s research development program in HDL modulation and obesity.
Dr. Gortler completed his fellowship training in Vascular
Medicine at the Yale School of Medicine where he conducted research in the area
of signal transduction of atheroprogression and vascular inflammation. Since
his graduation, Dr. Gortler has authored over 50 clinical trial protocols,
reports, and publications in the areas of cardiovascular disease, inflammation,
cholesterol metabolism, HDL modulation (CETP), obesity/weight loss, and drug
metabolism.
Research Background
on Atherosclerosis and Inflammatory Biomarkers:
Coronary artery disease remains the number one cause
of death and in a major cause of morbidity among men and women in the United
States.
Traditional risk factors for CAD include age, hypertension,
smoking, diabetes, elevated total cholesterol and decreased HDL. However
approximately 20% of cardiac events will occur in the absence of any of these
risk factors. Additionally, half of these events will occur in the absence of
any lipid abnormalities. Thus, existing biomarkers and risk stratification
guidelines could be better in predicting cardiovascular risk.
In vitro, HDL is thought to mediate the transport of excess cholesterol from
the periphery (including the arterial wall) to the liver and promotes efflux of
cholesterol from foam cells in atherosclerotic lesions (reverse cholesterol
transport).
Despite HDL’s inherent function as a cholesterol scavenger
and transporter, it remains an open question as to whether or not low HDL levels
are a causal risk factor for CHD, or if HDL may be used as a treatment target.
It is difficult to draw results data derived from HDL drug and lifestyle
intervention studies, because these studies tend to affect other risk factors
such as lipid components, and especially triglycerides. Observational studies
have shown that low HDL is associated with an increased risk for CAD, however in
the high HDL group there is not always a reduced risk.
It is now
understood that atherosclerosis is fundamentally an inflammatory disorder and
both lipids and inflammation need to be addressed simultaneously in order to
more accurately predict cardiovascular risk. It is now known that some of the
clinical benefits of HMG-CoA reductase inhibitors (statins) and angiotensin-converting
enzyme inhibitor therapy may derive from interrupting pro-inflammatory
pathways. With regards to atherosclerosis, the only biomarker we have data
available for is hsCRP. Research is ongoing for other inflammatory biomarkers.
Plaque Obstructed Coronary Artery
Patient Coronary Artery
Neuroendocrine
Signaling and Obesity/ Weight Loss Research:
The association between obesity and CAD is well
established, with weight reduction being one of the most important goals in the
treatment of atherosclerosis. The current epidemiological trend is producing
obesity at unprecedented rates and obesity and obesity- associated free radical
production are emerging as the most important contributors to increased
cardiovascular morbidity and mortality. Currently available pharmaceuticals
either alone or in combination have been shown to be only modestly effective in
treating weight loss, and even less effective for treating weight maintenance
following weight loss, which demonstrates that the causes of obesity are not
completely understood.
Considerable research is currently underway in both the causative and
curative aspects of obesity with respects to fat absorption, appetite
suppression, inflammation, lifestyle intervention and dieting in conjunction
with neuroendocrine signaling and protein signaling, in order to provide the
best palliation, treatment, care and prevention of obesity.
Basic Science
and Drug Development:
Dr. David Gortler's basic science research explores various
cell signaling pathways as related to heart disease, vascular wall thickening,
vascular inflammation, (TNF-alpha, IL-6, COX-2, LOX, PGE-2, MCP-1, M-CSF, and
VCAM-1) and the non-random localization of atherosclerotic plaques in the
vasculature. Considerable evidence suggests that impaired endogenous
atheroprotective mechanisms occur at branch points in arteries, where the
endothelial cells experience cyclic strain and shear stress. Pathways examined
include the signaling cascade along PI 3-kinase (akt/PKB, BAD, nf-Kb, others)
and their roles in hemodynamic stimuli as related to intimal hyperplasia, and
atheroma formation mediated through apoptotic pathways.
His clinical research involves the early- and late-phase review and
development of novel compounds which have the potential to modulate lipid
production, atheroprogression, vascular inflammation, HDL modulation, hsCRP,
weight loss, neuroendocrine signaling and related areas of metabolism and
endocrinology.
Medline Publications and Articles:
Click here to do a web search for all articles by David S. Gortler
Click here for publicly available full text articles by David Gortler
“Frontiers in Medicine” article and profile for David Gortler
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