Barbara Sherry, PhD, is currently a professor and head of the Center for Immunology and Inflammation at The Feinstein Institutes for Medical Research. She holds a joint appointment as professor in the departments of medicine and molecular medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell.
Dr. Sherry received her bachelor’s degree from Smith College and her doctoral degree from Brandeis University. Early in her career, while a postdoctoral fellow at The Rockefeller University, Dr. Sherry pioneered a protein-based strategy to discover novel cytokines – immune regulatory proteins secreted by blood cells – that play a role in protecting the body against pathogens. Her work led to the discovery of three novel proteins (MIP-1α, MIP-1β and MIP-2) whose actions are critical for both host defense and normal immune system homeostasis. These were three of the founding members of the group of proteins now known as chemokines – a class of secreted proteins that regulate cell movement and serve as the “traffic cops” of the immune system. Dr. Sherry’s laboratory continues to investigate the biological roles of these molecules in the body’s response to bacterial and viral infections and cancer.
Dr. Sherry is an international authority on chemokine biology and has authored more than 90 peer-reviewed publications in this field and has been an inventor or co-inventor on seven patents.
Her research has been funded by the National Institutes of Health and Concerned Parents for AIDS Research.
Dr. Sherry’s laboratory has had a long-standing interest in the mechanisms that coordinate the innate immune response — the body’s first line of defense against invading pathogens including bacteria, viruses, parasites and tumors. Early work led to the discovery of a novel set of chemoattractant proteins secreted by cells in response to bacterial challenge, and the determination that those proteins were in fact members of a larger family of proteins (the chemokine family) that plays a critical role in host defense and immune system homeostasis.
As with other inflammatory cytokines, the team now recognizes that excessive production of these same chemokine proteins and/or dysregulation of chemokine receptor expression can have harmful consequences and contribute to disease-associated pathology.
Their ongoing research goal is to gain a better understanding of the molecular mechanisms that regulate chemokine and chemokine receptor responses in healthy individuals, and to identify how these pathways are dysregulated in sepsis, HIV infection and chronic lymphocytic leukemia. Their studies will identify new therapeutic targets to restore immune function and improve clinical outcome in disease.
One of the principal complications of sepsis syndrome, a potentially lethal illness triggered by systemic bacterial infection, is increased susceptibility to secondary lung infections. Macrophages are known to play an essential role in the resolution phase of pulmonary infection, and they are recruited to the lung by chemokine/chemokine receptor interactions. Dr. Sherry’s team’s studies have shown that exposure of macrophages to LPS, a major constituent of gram-negative bacteria, downregulates a subset of chemokine receptors, thereby markedly impairing the ability of affected cells to migrate in response to chemokine signals.
They are currently using dominant negative mutant, siRNA, and pharmacologic inhibitor strategies to elucidate the mechanisms that contribute to LPS-triggered downregulation of chemokine receptors in macrophages. To establish a link between chemokine receptor impairment and increased susceptibility to secondary infection in patients with sepsis, they are collaborating with Dr. Dana Lustbader and Dr. Marcia Epstein at Northwell Health to assess whether chemokine receptor expression and/or function are suppressed in circulating leukocytes isolated from septic patients, and if so, to evaluate whether these defects correlate with increased susceptibility to secondary lung infection and other sepsis-associated pathologies.
The results gained from this study will improve the team’s understanding of chemokine/chemokine receptor interactions within the context of sepsis, provide valuable insight into sepsis-associated immunosuppression and encourage the development of new therapeutic strategies to prevent and control secondary lung infections in sepsis. In complementary studies, they are exploring whether impaired chemokine-mediated cell trafficking contributes to other clinical syndromes that are associated with increased susceptibility to infection, including end-stage renal disease.
Chronic lymphocytic leukemia (CLL) is a B-cell malignancy that is characterized by the accumulation of monoclonal CD5+ B cells in the blood and tissues. Signals provided by the microenvironment are known to greatly influence the growth and survival of CLL cells. Some of these conditioning signals are provided by chemokines, a family of chemotactic proteins that play a role in host defense and immune system homeostasis, as well as other immune and inflammatory cytokines.
Dr. Sherry’s team is currently collaborating with Dr. Nicholas Chiorazzi and members of the CLL Research and Treatment Program at The Feinstein Institutes to better understand the role of chemokine and cytokine signals in the growth and survival of CLL cells. They have recently discovered that a subpopulation of T lymphocytes, Th17 cells, is elevated in the cohort of CLL patients who have prognostic markers that predict longer survival. Th17 cells are known to play a key role in inflammatory and autoimmune diseases, but had not previously been shown to have relevance in CLL. Current studies are focused on further elucidating the role of the Th17/IL-17 axis in CLL.
Paradoxically, chemokine receptors, critical for the transduction of intracellular signals that promote innate immune responses, are sometimes used by intracellular pathogens to facilitate their entry into cells and/or their transmission. Seminal studies by others revealed that a subset of chemokine receptors function as co-receptors for HIV-1, and that chemokines (the natural ligands for one of the HIV-1 co-receptor CCR5) exert potent anti-viral effects in T cells, presumably through their ability to interfere with viral co-receptor usage.
Numerous reports indicate that chemokine responses are defective in HIV-infected individuals, although the molecular basis for this defect is not fully understood. Dr. Sherry’s current studies focus on identifying cellular and molecular mechanisms whereby HIV-1 manipulates host anti-viral β-chemokine responses to its own benefit and assessing whether dysregulated chemokine responses may underlie abnormal cellular trafficking and impaired immune responses in patients with AIDS.
They have recently identified a previously unrecognized mechanism by which HIV type 1 (HIV-1) subverts the innate immune response – a discovery that they hope may open the door to the development of new therapeutic strategies to improve immune function in HIV-1-infected individuals.
Pui Yan (Paulina) Chiu, MS, MBA
Education: BS in Biology, 1990, King College; MS in Nutrition, 1993, Pennsylvania State University; MBA in Health Services Management, 2008, Hofstra University
Research: Elucidation of the molecular mechanisms regulating LPS-triggered chemokine receptor downregulation in macrophages; Characterization of chemokine responses in patients with sepsis, end stage renal disease, and HIV infection.
Email: [email protected].edu
Darren Hirsch, MD
T32 Fellow, Immunology Physician Scientist Program
Education: B.S. in Biology, 2005, Haverford College; MD, 2009, Jefferson Medical College; Internship and Residency in Internal Medicine, 2009-2012, Brown University
Research: Determination of the influence of Th17 cells on leukemic cell growth, survival, and trafficking in chronic lymphocytic leukemia (CLL).
Email: [email protected]
Erica K. Spessot
Admin Support Associate
Phone: (516) 562-1637
Email: [email protected]
Field of Study: Microbiology
Field of Study: Biochemistry