Raouf A. Khalil, MD, PhD, Awarded a $2.1M National Institutes of Health Grant

Raouf A. Khalil, MD, PhD, has been awarded a National Institutes of Health (NIH) grant for his study “Vascular mechanisms of hypertension-in-pregnancy.”

Normal pregnancy is associated with increased cardiac output and decreased vascular resistance in order to maintain adequate blood supply to the developing fetus. These beneficial hemodynamic changes do not occur in women with preeclampsia. Preeclampsia is a complication of pregnancy characterized by hypertension and fetal growth restriction; however, the underlying mechanisms are unclear. Reduction in uterine perfusion pressure and the ensuing placental ischemia/hypoxia trigger the release of placental factors such as TNF-alpha and reactive oxygen species. 

The objectives of Dr. Khalil’s study are to understand how the release of placental factors could lead to endothelial cell dysfunction and reduction in vasodilator substances such as nitric oxide and prostacyclin and to test the hypothesis that an imbalance between vasodilator matrix metalloproteinases MMP-2 and -9 and vasoconstrictor MMP-1 and -7 triggered by an upstream increase in ADAM-17 activity is a major mechanism of inadequate uteroplacental remodeling and vascular dysfunction in hypertension in pregnancy. Disruption of the vasodilator/vasoconstrictor MMP balance results in inadequate uteroplacental remodeling, decreased vasodilation, increased vasoconstriction and hypertension in pregnancy.

Consequently, correcting MMP imbalance by upregulating vasodilator MMP-2 and -9, or downregulating vasoconstrictor MMP-1 and -7 or reducing the upstream ADAM-17 activity should improve uteroplacental remodeling, promote vasodilation, and reduce vasoconstriction and hypertension in pregnancy, and thereby provide a new approach for the management of preeclampsia.

Raouf A. Khalil, MD, PhD
Lead Investigator, Division of Vascular and Endovascular Surgery, Vascular Surgery Research Laboratories, Brigham and Women’s Hospital
Associate Professor, Harvard Medical School

Dr. Khalil received his medical degree from Cairo University and a master’s in pharmacology from Assiut University. He then completed his PhD in vascular pharmacology at the University of Miami School of Medicine. After completing his postdoctoral training at Harvard University and Beth Israel Hospital, he joined the faculty in the Department of Physiology at the University of Mississippi Medical Center. Dr. Khalil joined the Department of Surgery at the Brigham in 2004 and has since demonstrated excellence in research and teaching programs for the past 15 years.

His achievements have been recognized for his important contributions in the field of vascular surgery research, his scholarly reputation and his involvement in teaching programs. He is a highly productive, nationally recognized investigator in the field of smooth muscle physiology who has made important contributions as a scientist and educator. Dr. Khalil has authored more than 170 peer reviewed publications in several highly respected scientific journals. He has served as editor, editorial board member and reviewer on more than 100 scientific journals. Dr. Khalil has served as a member of numerous National Institutes of Health (NIH) and American Heart Association (AHA) study sections and several international grant review panels. He has also mentored more than 160 postdoctoral fellows and graduate and undergraduate students.  

Dr. Khalil’s major research interests include smooth muscle physiology and pharmacology, pathophysiology of vascular restenosis, coronary artery disease, essential hypertension, and hypertension-in-pregnancy and preeclampsia. He has been interested in understanding the mechanisms of vascular smooth muscle contractility and growth, Ca2+ -dependent and Ca2+ -independent mechanisms of cell activation, Ca2+ homeostasis in living cells, signal transduction, G proteins, protein kinase C and kinase cascades. His laboratory uses state-of-the-art technology for measurement of vascular function and signaling utilizing advanced physiological assays, molecular biology techniques, fluorescent probes, immunofluorescence and immunocytochemistry, digital imaging microscopy and confocal microscopy. His research has been continuously funded since 1991 by grants from the AHA and the NIH/National Heart, Lung, and Blood Institute (NHLBI).

Dr. Khalil’s research has been centered on several funded projects, including “Mechanisms of gender-specific differences in vascular tone in hypertension,” “Vascular protective role of endothelin B receptors during high salt diet,” “Vascular angiotensin type-2 receptor in normal and hypertensive pregnancy,” “Role of endothelin B receptor in vascular protection in females,” “Mechano-sensitive hypoxia-inducible factor-MMP pathway in venous insufficiency,” “Evaluation of sulodexide in the modulation of matrix metalloproteinases and their effects on venous endothelial and smooth muscle function” and “Vascular mechanisms in pregnancy-induced hypertension.”

2020 Final Service Conference and Graduation Awards

The following recipients were recently honored with awards at the Final Service Conference.

Student Teaching Awards           

  • PGY 1: Cullen Roberts, MD
  • PGY 2: James Etheridge, MD
  • PGY 3: Sasha Mahvi, MD
  • PGY 4: George Li, MD
  • PGY 5: Kristin Sonderman, MD (Recipient of the Robert T. Osteen Award for Medical Student Education in Surgery)

Surgery Class of ’63 Scholar: Heather Lyu, MD

PBB Scholar Award: George Li, MD

Grant Rodkey Award (VA Hospital Award): Rhea Udyavar, MD

Christine Weeks Schofield Award (South Shore Hospital Award): James Etheridge, MD

Edward Kwasnik Award (South Shore Hospital Award): Bryan Dieffenbach, MD

The Vollman Award (Faulkner Hospital Award): Elizabeth Yates, MD

Starfish Award: Sasha Mahvi, MD

Francis D. Moore, Sr. Award: David Harris, MD

Donald D. Matson Award: Christopher Burns, MD

Richard E. Wilson Award: Thomas Clancy, MD

Stefan G. Tullius, MD, PhD, Awarded $2.5M National Institutes of Health Grant

Stefan G. Tullius, MD, PhD, has been awarded a National Institutes of Health (NIH) grant for his study “Senescent cells drive mt-DNA accumulation and inflamm-aging.”

The sharp discrepancy between demand and supply of organs causes high mortality and morbidity rates in waitlisted patients. Organ transplantation is hampered by a limited supply of organs, with many patients waiting for numerous years and numerous patients dying before getting a transplant. The aging population is also on the rise, and although organs from older donors are available, they are frequently not considered or discarded with concerns of compromised function and augmented immunogenicity. With aging, senescent cells accumulate, producing increasing amounts of inflammatory products.

This grant will delineate specific immune responses when transplanting older organs. Dr Tullius and his group will test if the depletion of senescent cells through senolytics will improve transplant outcomes and modify immune responses. The proposal will also test if senescent cells will be transferred in organ transplants and if those senescent cells will impact aging. As donor and recipient ages may vary substantially, it is also possible that aging processes in transplant recipients may be either accelerated or that the transplantation of a younger organ will slow aging. The supported research may help to increase the availability of organs for transplants, delineate organ-age specific immune responses and determine the fate of senescent cells transferred with organ transplantation.  Optimizing the utilization and outcomes of older transplanted organs is also expected to reduce mortality and morbidity rates of waitlisted patients with end-stage organ failure.

Stefan G Tullius, MD, PhD
Chief, Division of Transplant Surgery, Brigham and Women’s Hospital
Professor of Surgery, Harvard Medical School
Director, Transplant Surgery Research Laboratory

Dr. Tullius is the chief of the Division of Transplant Surgery at Brigham and Women’s Hospital and a professor of surgery at Harvard Medical School. He received his medical degree from the Johann-Wolfgang Goethe University in Frankfurt, Germany; a PhD from the Charité in Berlin, Germany; and a (honorary) Master of Arts from Harvard University.  He has published over 280 peer-reviewed articles, led numerous externally funded studies, and is frequently invited to speak locally, nationally, and internationally.

His research career in transplantation immunology covers a period of more than 15 years and has greatly contributed to an improved understanding of the pathophysiology of long-term graft failure. His more recent research interests include individualized immunosuppression and the investigation of basic mechanisms of clinically relevant aspects in organ transplantation, focusing on novel routes for optimized utilization of organs for transplantation and organ preservation/perfusion. Dr. Tullius has also contributed with pioneering work in face, hand and uterus transplantation.

In addition to his clinical practice and research interests, Dr. Tullius has contributed to the international transplant community with his editorial, societal and committee activities. He is an executive editor of Transplantation, associate editor of Transplant International, and has served as associate and consulting editor of the American Journal of Transplantation. He has also served on the board of the European Society for Organ Transplantation (ESOT) and was the founding chair of the Basic Science Committee of ESOT. He has co-chaired several international meetings for The Transplantation Society (TTS), chaired several committees for the American Society of Transplantation (AST) and was the founding chair of the AST Vascular Composite Tissue Transplant Committee.

Dr. Tullius is currently a member of the Declaration of Istanbul Custodian Group (DICG), the senior treasurer of TTS and vice president of the International Society of Uterus Transplantation (ISUTx). In recognition of his contributions, Dr. Tullius has received several awards, including the Clinical Science Investigator Award of the AST, the Joseph E. Murray and Simon J. Simonian Award and the Excellence in Kidney Transplantation Award by the National Kidney Foundation.