When blood vessels break, platelets stop the bleeding by adhering to the damaged vessel walls. They aggregate with each other and facilitate thrombin production and fibrin deposition, both of which are key components of blood coagulation. Dr. Coller’s research focuses on molecular interactions between blood cells and blood vessels as they relate to platelet physiology, thrombosis, vascular biology and adhesion phenomena, with the ultimate goal of developing new therapies for thrombosis and sickle cell disease.
Because platelets play a vital role in blood coagulation, deficiencies in their numbers or function can result in excessive bleeding. But when platelets adhere to and aggregate on blood vessels narrowed by atherosclerosis, they can close off the blood vessel and cause a myocardial infarction (heart attack) or stroke.
By studying the receptors responsible for platelet aggregation, and patients who genetically lack the receptors, Dr. Coller established the platelet 
IIb
3 (GPIIb/IIIa) receptor as an important target for antithrombotic therapy. This led him to develop monoclonal antibodies to the IIb3 receptor that inhibited platelet aggregation. Working with scientists at Centocor, Dr. Coller helped develop one of these antibodies into the drug abciximab, which was approved in 1994 to prevent ischemic complications of percutaneous coronary interventions, such as stent placement in patients with myocardial infarction and related conditions. More than two and a half million patients worldwide have been treated with abciximab.
Current research in Dr. Coller’s lab focuses on multiple areas of platelet physiology. One of those areas is the genetic disorder Glanzmann thrombasthenia, which produces hemorrhage as a result of an abnormality of the IIb3 receptor. Dr. Coller and his lab members are studying the precise genetic and protein abnormalities responsible for the disease.
Other areas of blood and platelet physiology that the lab is studying include:
1. Integrin structure and activation: Integrins (including IIb3) are transmembrane glycoprotein receptors. Through site-directed mutagenesis and molecular dynamics studies, the lab is studying the mechanisms by which the receptors undergo a transition from an inactive to an active conformation with high affinity for ligand. The atomic interactions between the receptor and the ligand are also being evaluated, as are the changes induced when ligand binds to the receptor.
2. High throughput screening: The Coller lab has identified a single compound out of more than 33,000 tested that inhibits ligand binding to IIb3. This lead is being pursued by chemical modifications to enhance affinity and as a structural probe of the IIb3 ligand binding pocket.
3. Platelet TGF1: The Coller lab is studying the mechanism(s) by which TGF1, a potent modifier of gene transcription and cellular behavior, is activated and the effects of the active TGF1 in wound healing and thrombosis.
4. Adhesion in sickle cell disease: The Coller lab is looking into the molecular basis of the interactions among sickle cell erythrocytes, leukocytes, endothelial cells and platelets
so as to develop therapeutic interventions that diminish the vascular complications of the disease.
5. Murine models of myocardial infarction:
To better study myocardial infarction in mice, the Coller lab is using ultrasound-guided techniques to induce myocardial
infarction that are less traumatic than current surgical methods.
CAREER
Dr. Coller received his B.A. from Columbia
University in 1966 and his M.D. from New
York University School of Medicine in 1970. He
completed his residency in internal medicine at
Bellevue Hospital in New York City and received
advanced training in hematology and clinical
pathology at the National Institutes of Health.
He was at Stony Brook University from 1976
to 1993, and from 1993 to 2001, Dr. Coller
served as a professor of medicine and chairman
of the department of medicine at Mount Sinai
School of Medicine. He came to Rockefeller in
2001 as the first David Rockefeller Professor
of Medicine, head of the Laboratory of Blood
and Vascular Biology, physician-in-chief of The
Rockefeller University Hospital and vice president
for medical affairs. Dr. Coller also serves as
principal investigator of the university’s Clinical
and Translational Science Award and director of
The Rockefeller University Center for Clinical
and Translational Science.
Dr. Coller received the Robert J. and Claire
Pasarow Foundation Award in 2005, the
Warren Alpert Foundation Award in 2001
and a National Research Achievement Award
from the American Heart Association in 1998.
He is a member of the Institute of Medicine,
the National Academy of Sciences and the
American Academy of Arts and Sciences.
