Nathan I. Shapiro, M.D., M.P.H.
Director of Translational Research, CVBR
Beth Israel Deaconess Medical Center
Harvard Medical School
330 Brookline Avenue, RN-234
Boston, MA 02215
Dr. Shapiro received his medical degree from Temple University School of Medicine, completed an internship year in transitional medicine at Cook County Hospital, followed by residency in Emergency Medicine at the Harvard Affiliated Emergency Medicine. He then received a masters in public health degree in clinical effectiveness from the Harvard School of Public Health. He is currently an attending physician in the Department of Emergency Medicine at Beth Israel Deaconess Medical Center, and an Assistant Professor of Medicine at Harvard Medical School, and joined to Center for Vascular Biology Research two years ago with a focus on propagating translational research.
Research Interests: Endothelial cell dysfunction in sepsis
Translational Research - Endothelial Cell Signaling in Murine Sepsis. We are currently working towards an improved understanding of endothelial cell signaling in sepsis. Having observed increased circulating levels of endothelial cells biomarkers in humans with sepsis, we are returning to the bench to better understand the pathophysiology of the host response. Specifically, we are currently exploring the protein expression by the endothelium on the skin surface based on the hypothesis that the endothelium is a disseminated target organ, and the skin is a potentially valuable window that could be used to assess the state of the host response.
Clinical Research - Endothelial Cell Signaling in Human Sepsis. We have recently received funding from National Heart Lung and Blood Institute to study endothelial cell signaling through assays of a panel of circulating endothelial cell related biomarkers. The overall hypothesis of this project is that severe sepsis is associated with endothelial dysfunction; which, in turn, is predictive of subsequent organ failure and death; and that protocolized resuscitation attenuates endothelial cell (EC) dysfunction and improves patient survival. The overall goal of this project is to study the role of the endothelium in sepsis in a large, heterogeneous group of patients who are being enrolled in the Protocolized Care in Early Severe Sepsis (ProCESS) trial. ProCESS is a NIH-funded 1,950 subject randomized, multi-center, clinical trial comparing resuscitation strategies in sepsis that has recently initiated enrollment.
Microcirculatory Flow in Sepsis. As part of the above mentioned multicenter trial we will use sidestream darkfield imaging to visualize and quantify microcirculatory flow using a handheld bedside videomicroscope. By visualizing the flow through the smallest vessels in the sublingual circulation, we will assess the relationship between microcirculatory flow, organ dysfunction, and mortality, as well as the relationship between endothelial cell signaling and microcirculatory flow. Skin Biopsies to quantify endothelial cell protein expression in human sepsis. As a complimentary study to our pre-clinical investigation, we will perform skin biopsies and examine protein expression on the endothelial cell surface by key biomarkers. We will explore the utility of skin biopsies to assess host response in sepsis.
New and Noteworthy Publications:
Shapiro NI, Wolfe RE, Moore RB, Smith L, Burdick E, and Bates DW. “Mortality In Emergency Department Sepsis (MEDS) Score: A Prospectively Derived and Validated Clinical Prediction Rule.” Critical Care Medicine. Mar 2003;31(3):670-675. This study describes a novel and highly effective system for targeted delivery of siRNA to selected tissues in vivo that may have broad application as both an experimental tool and therapeutic strategy.
Shapiro NI, Howell M, Talmor D, Lahey D, Ngo L, Wolfe RE, Weiss JW, Lisbon A. Implementation and Outcomes of the Mutliple Urgent Sepsis Therapies (MUST) Protocol. Crit Care Med. 2006 Apr; 34 (4): 1025-1032. This well cited study established a severity of illness scoring system for emergency department patients with suspected infection.
Shapiro NI, Howell M, Talmor D, Lahey D, Ngo L, Wolfe RE, Weiss JW, Lisbon A. Implementation and Outcomes of the Mutliple Urgent Sepsis Therapies (MUST) Protocol. Crit Care Med. 2006 Apr; 34 (4): 1025-1032. This study establishes the feasibility of implementing an integrated sepsis protocol, and its ability to facilitate a more aggressive resuscitation.
Shapiro NI, Howell MD, Bates DW, Angus DC, Ngo L, Talmor D. The Association of Sepsis Syndrome and Organ Dysfunction with Mortality in Emergency Department Patients with Suspected Infection. Ann Emerg Med. 2006 Nov;48(5):583-90. The sepsis syndromes are reported in association with their clinical outcomes in the emergency department, along with the importance of organ dysfunctions in sepsis.
Howell MD, Donnino M, Talmor D, Clardy P, Shapiro NI. Occult Hypoperfusion and Mortality in Patients with Suspected Infection. Intensive Care Medicine. 2007 Jul 6; [Epub ahead of Print]. The predictive ability of serum lactate is established with consideration of hemodynamic and other clinical variables.
Shapiro NI, Yano K, Okada H, Fischer C, Howell M, Spokes KC, Ngo L, Angus DC and Aird WC. A Prospective, Observational study of Soluble FLT-1 and Vascular Endothelial Growth Factor (VEGF) in Sepsis. Shock. 2007 Aug 16; [Epub ahead of Print]. The association of VEGF and sFLT-1 with organ dysfunction, shock, and markers of inflammation are reported in emergency department patients with suspected infection.