Platelet aggregation and mental stress induced myocardial ischemia: Results from the Responses of Myocardial Ischemia to Escitalopram Treatment (REMIT) study.

My research program investigates the molecular mechanisms whereby various congenital and acquired abnormalities result in ‘dysfunctional’ hemostasis (i.e., hemorrhage or thrombosis) to better understand the molecular mechanisms and interactions that are necessary for normal hemostasis. We are particularly interested in the mechanisms whereby antibodies and other inhibitors can interfere with normal hemostatic mechanisms. Several projects extensively overlap and focus on the assembly and function of procoagulant (e.g., factor X-ase and prothrombinase) and anticoagulant (e.g., activated protein C complex) phospholipid membrane-dependent complexes.

We utilize a variety of approaches in these studies. Monoclonal antibodies, single-chain variable domain fragments, polyclonal antibodies prepared from patients with factor VIII inhibitors, and site-specific mutagenesis have all been used to characterize structure-function relationships in coagulation factor VIII. Our laboratory has also extensively characterized anti-factor V antibodies, investigating autoantibodies as well as xenogenic antibodies developing after exposure to topical bovine thrombin preparations which contain trace amounts of contaminating bovine factor V. We have also characterized how antiphospholipid antibodies interfere with the activated protein C complex, a lipid-dependent natural anticoagulant complex that proteolytically inactivates factor Va and factor VIIIa.

Our current studies are focusing on two antibody-mediated thrombotic syndromes, heparin-induced thrombocytopenia and antiphospholipid antibody syndrome. First, we are initiating a large clinical trial investigating the incidence of clinically-significant heparin-induced thrombocytopenia in patients who develop anti-heparin/platelet factor 4 antibodies following cardiac bypass procedures. While these antibodies are commonly seen following cardiac bypass, the true incidence of thromboembolic complications related to these prothrombotic antibodies remains unknown. We are also collaborating with investigators in the Center for Human Genetics on a large, multi-center study exploring the genetics of familial antiphospholipid antibody syndrome. In addition, we have used a genomic strategy to investigate patients with antiphospholipid antibody syndrome and have identified a gene expression profile that appears to be unique to patients with this syndrome in contrast to patients with venous thromboembolism who do not have these autoantibodies.

We also participate in a variety of collaborative research efforts, both with individual investigators as well as participating in multi-center clinical research studies. For example, we are one of seventeen centers participating in the NIH-supported Transfusion Medicine/Hemostasis Network, and we are currently conducting a trial through this network to define the optimal dose of platelets for patients needing platelet transfusions for hypoproliferative thrombocytopenia. We are also part of a multi-center registry of patients with thrombotic thrombocytopenic purpura, and we are one of eight centers in the Hemostasis and Thrombosis Center pilot program sponsored by the Centers for Disease Control and Prevention. Participation in these registries and networks provides us with access to the patient populations that we study in the research laboratory.

Dr. Zainab Samad is chairwoman of the Department of Medicine at Aga Khan University (AKU) in Pakistan and currently serves as an Adjunct Associate Professor of Medicine at Duke University. 

She attended Medical School at the Aga Khan University Medical College in Karachi, Pakistan and thereafter completed her residency training in Internal Medicine and fellowship in Cardiology at Duke University Medical Center in Durham, North Carolina. Additionally, she completed advanced training in cardiovascular imaging, specifically in clinical echocardiography, cardiac MRI and SPECT-myocardial perfusion imaging. She is also trained in quantitative methods with a Master of Health Sciences in Clinical Research degree from the National Institutes of Health- Duke Clinical Research Training Program. She served on faculty in the Division of Cardiology, Department of Medicine for nine years before accepting the position at AKU in 2018. She resides full-time in Karachi.

This laboratory uses a multidisciplinary approach using both animal and model systems to study the biology of addiction and stress/depression. We are specifically interested in how adolescence and the hormonal changes of puberty and aging influence vulnerability to these conditions. Specific projects underway include: (1) the biology of sex differences in addictive drug action, (2) role of maturing dopamine systems in the onset of drug taking during adolescence, (3) the neurobiology of adolescent insensitivity to threat and its role in drug use.
Studies of sex differences focus on understanding estrogen and testosterone actions in the brain that are relevant to addiction, depression and stress-related behaviors. We are particularly interested in molecular targets of estrogen action including key proteins that regulate dopamine neurons and the stress peptide CRF. Current projects include the role of glucocorticoid and reproductive hormones in alcohol and opioid dependence in adolescence.  Adolescent studies are exploring the impact of maturing dopamine systems as well as cortical inhibition of these systems on novelty-seeking/risk taking as predictors of substance abuse vulnerability as well as responses to addictive drugs.
In addition to these animal studies, we collaborate actively with clinicians in psychiatry who are studying addiction and stress-related illness in humans, and participate in development of drug-abuse education and general neuroscience education materials for students, parents and other members of the lay public.

My research aims to identify psychosocial factors that are involved in the pathogenesis and course of major medical disorders, to characterize the biobehavioral mechanisms whereby such factors influence disease, and to develop both behavioral and pharmacologic means of preventing or ameliorating the adverse impact of psychosocial factors on health and disease. Specific projects that are currently active include: 1) The influence of hostile personality, social isolation, depression and other psychosocial risk factors upon the development and course of cardiometabolic disease; 2) Biological and genetic mechanisms whereby psychosocial risk factors influence disease development and course; and 3) Behavioral and pharmacologic approaches to ameliorate impact of psychosocial risk factors on disease risk and course.