Education

Degree	Institution	Major
BS	University of Notre Dame	Microbiology
MS	University of Michigan	Microbiology and Immunology
PhD	University of Michigan	Microbiology and Immunology

Post-Graduate Training

Training	Institution	Specialty
Postdoctoral	National Institute of Allergy and Infectious Diseases	Immunology
Postdoctoral	University of Michigan	Human Genetics

Awards

Name of Award/Honor	Awarding Organization
North American Vascular Biology Annual Meeting - Roundtable Discussion of Cell-Matrix Interactions in Vascular Remodeling	North American Vascular Biology Meeting
Connecticut Academy of Science and Engineering Member	CASE
GWIMS Mentoring Award	GWIMS
Outstanding Scientist Award	GWIMS
National Research Service Award, 1986-1988	National Institutes of Health
Thurnau Postdoctoral Fellowship 1985-1986	University of Michigan
Damon Runyon-Walter Winchell Cancer Fund Fellowship 1984-1985	Damon Runyon Cancer Research Foundation

Name & Description	Category	Role	Type	Scope	Start Year	End Year
Reviewer- Pharmacy Interdisciplinary Grants	Study Section	member	UConn-Storrs	State	2020	2020
Reviewer- Keck Research Grant Program	Study Section	member	UConn-Storrs	National	2020	2020
Public Issues Council	Advisory Committee	member	UConn Health	Regional	2019
Department of Immunology Review	Advisory Committee	member	UConn Health	Local	2019	2019
Vascular Biology Publications Alert	Advisory Committee	Editor	External	International	2019
Search Committee, CCAM Director	Advisory Committee	member	UConn Health	Local	2019
Council Member- North American Vascular Biology Organization (NAVBO)	Advisory Committee	member	External	International	2019
Co-chair, Block Symposium “Leukocyte adhesion and migration" 2018 American Association of Immunology annual meeting, Austin Texas May 4-8, 2018.	Professional/Scientific Organization	co-chair	External	National	2018	2018
Senior Appointments and Promotions Committee	Advisory Committee	Secondary Reviewer	UConn Health	University	2017
NIDDK Review of O'Brien Kidney Research Grants	Study Section	member	External	National	2017	2017
VCMB Study Section	Study Section	ad-hoc member	External	National	2017	2017
Search Committee, Chair of Neuroscience	Advisory Committee	member	UConn Health	National	2017	2017
Education Committee, North American Vascular Biology Association	Education Committee	Member	External	International	2016	2019
Research Council	Research Committee	member	UConn Health	University	2012
CCESC	Education Committee	Member	UConn Health	University	2011
Graduate Women in Medicine and Science Steering Committee, UCHC	Advisory Committee	Member	UConn Health	University	2011
Ad Hoc PPG Review	Study Section	Reviewer	External	National	2010	2011
Cell Biology Graduate Program	Advisory Committee	Assistant Director	UConn Health	University	2009	2010
American Association of Immunologists	Professional/Scientific Organization	member	External	National	2008
Journal of Biological Chemistry	Editorial Board	Member	External	National	2007	2012
Atherosclerosis and Inflammation in the Cardiovascular System study section, (AICS) NIH	Study Section	Member	External	National	2006	2011
Leukemia, Immunology, and Blood Cell Development Peer Review Committee, American Cancer Society	Advisory Committee	Member	External	National	2003	2006
Graduate School Admissions Committee	Advisory Committee	Member	UConn Health	University	2001
Graduate Program Committee	Advisory Committee	Member	UConn Health	University	2001	2009
Blood	Professional/Scientific Journal	Reviewer	External	National
Molecular and Cellular Biology	Professional/Scientific Journal	Reviewer	External	National
Leukemia	Professional/Scientific Journal	Reviewer	External	National
Experimental Cell Research	Professional/Scientific Journal	Reviewer	External	National
Oncology	Professional/Scientific Journal	Reviewer	External	National
Cancer Research	Professional/Scientific Journal	Reviewer	External	National
Cell Growth and Differentiation	Professional/Scientific Journal	Reviewer	External	National
Journal of Cellular Biochemistry	Professional/Scientific Journal	Reviewer	External	National
Journal of the National Cancer Institute	Professional/Scientific Journal	Reviewer	External	National
Oncogene	Professional/Scientific Journal	Reviewer	External	National
Immunology	Professional/Scientific Journal	Reviewer	External	National
Clinical and Experimental Immunology	Professional/Scientific Journal	Reviewer	External	National
Gene	Professional/Scientific Journal	Reviewer	External	National
Biotechniques	Professional/Scientific Journal	Reviewer	External	National
International Journal of Cancer	Professional/Scientific Journal	Reviewer	External	International
Atherosclerosis, Thrombosis, and Vascular Biology	Professional/Scientific Journal	Reviewer	External	National
Biochemical Journal	Professional/Scientific Journal	Reviewer	External	National
National Science Foundation	Professional/Scientific Organization	Reviewer	External	National
Veterans Administration Merit Award	Advisory Committee	Reviewer	External	National
Stem Cell Research and Therapy	Professional/Scientific Journal	reviewer		National
Public Issues Council	Research Committee	member	UConn Health	Regional

Research in the Shapiro laboratory concentrates on understanding the regulation and function of cell surface peptidases in the angiogenic endothelium of tumors, vessels at sites of inflammation and in cardiovascular disease. Numerous cell surface peptidases are strikingly upregulated on angiogenic endothelial cells leading to the hypothesis that these may functionally cooperate in enzymatic cascades to regulate angiogenesis and endothelial cell function. While the angiogenic significance of proteases that cleave large proteins (such as the matrix metalloproteases) is well documented, increasing evidence supports a role for peptidases (metAP2, CD13, APA, PSMA) as angiogenic regulators as well. The fact that these enzymes metabolize small peptide substrates suggests that small molecule regulators of angiogenesis exist which have yet to be identified and whose mechanisms are unknown. Indeed, we have shown that individually, two peptidases, CD13 and PSMA are potent regulators of angiogenesis and our investigation of their regulatory mechanisms and their possible interaction is the current focus of the laboratory.We have shown that inhibition of CD13/APN blocks endothelial morphogenesis and invasion and we continue to examine the molecular mechanisms responsible for its angiogenic regulatory capabilities, particularly its role in invasion. Recent studies from our lab suggest that CD13 regulates signal transduction pathways leading to invasion by participating in plasma membrane organization via its interaction with membrane cholesterol. Further investigations have indicated that CD13 also functions as an adhesion molecule where it mediates inflammatory cell interactions as well as endothelial/extracellular matrix interactions in a signal transduction dependent manner which has strong implications for regulation of inflammatory leukocyte trafficking and angiogenic cell invasion. Furthermore, CD13 is expressed on adult pluripotent stem cells and may play a role in stem cell trafficking as well. Finally, high levels of CD13 are found in the serum of patients with certain types of cancers and inflammatory diseases and we are currently investigating the mechanisms regulating its release from the cell surface and CD13’s utility as a serum biomarker of chemoprevention in breast cancer and myocardial infarction. We have recently produced a conditional CD13 knockout mouse and are actively characterizing CD13’s contribution to various physiologic and pathologic processes by specifically inactivating the gene in specific tissues.Our investigation into the function of a second cell surface peptidase, PSMA has shown that this peptidase also regulates cell signaling, albeit by an apparently different mechanism. Investigation of PSMA’s regulation of endothelial cell adhesion led to the very interesting discovery that PSMA is a component of a complex regulatory loop that controls integrin signaling and PAK1 activation. Invasion studies with PSMA-null cells showed that PSMA regulates cell invasion by controlling signaling from beta1 integrins to focal adhesion kinase (FAK) and PAK1. We showed that PSMA interacts with the actin-binding protein filamin A, and disruption of this interaction decreases the peptidase activity of PMSA and phosphorylation of PAK1 in cultured cells. The interaction of PMSA with the cytoskeleton via filamin A allows a feedback signal from integrin beta1 and PAK that holds PMSA activity in check. Inhibition of PAK by expression of a peptide corresponding to its autoinhibitory domain enhanced the association of PMSA with filamin A, thus increasing its peptidase activity. These studies suggest an extracellular matrix derived, small molecule PSMA substrate that superactivates beta1 integrins, thus regulating angiogenesis and cell invasion. The manuscript describing this work was recently featured as a ‘highlight of the recent literature’ by the editors of Science.Investigation into the regulation and function of these molecules will increase our understanding of molecular mechanisms controlling blood vessel formation in a variety of diseases such as cancer, heart disease, inflammatory disorders, diabetic retinopathy, and arthritis.Future Directions We will extend the laboratory’s observations on the roles of cell surface peptidases in various pathologic states. We have conditional CD13 knockout animals and complete PSMA knockouts, so both in vitro and in vivo studies are feasible. For CD13, experiments will be directed toward its role as an adhesion molecule on endothelial cells and monocytes and its potential regulation of inflammation, inflammatory diseases and cancer. Specific areas of research will elucidate its interacting adhesion partners, its place in the established paradigm of leukocyte trafficking, characterization of the signal transduction cascades induced by CD13 and investigation of its internalization and re-expression on the membrane. In addition, studies will continue on the mechanism of CD13 shedding and the function of soluble CD13 in inflammation and stem cell trafficking. Studies regarding PSMA will focus on its role as an angiogenic regulator and its control of cell invasion via integrin signaling. Specifically we will concentrate on identifying its angiogenic/integrin activating peptide substrate, the concept of regulation of angiogenesis by small extracellular matrix derived-peptide fragments and the role of PSMA in prostate tumorigenesis and invasion.

Accepting Lab Rotation Students: Fall Block 2024, Spring 1 and 2 Block 2025

Journal Articles

Book Chapters

Letters

Other

Reviews

Title or Abstract	Type	Sponsor/Event	Date/Year	Location
CD13 controls myeloid cell cell fusion. Authors- Mallika Ghosh, F. Mcgurk, S. Nair, K. Morais, L. Shapiro	Poster		2022
Seventeenth Annual New England Science Symposium CD13 Promotes Tunneling Nanotube Formation and Cell-cell Communication in Human Endothelial Cells and Mouse Primary Macrophages Brian Aguilera, Linda Shapiro and Mallika Ghosh	Poster	New England Science Symposium	2018	Harvard Medical School, Boston, MA
Renal CD13/aminopeptidase N: Brush Border Peptidase, Regulator of Albumin Uptake and Potential Urinary Biomarker	Talk	New York Medical College	2017	Valhalla, NY
CD13 is a Regulator of Cell-ECM Adhesion	Talk	University of Washington School of Public Health	2017	Seattle, WA
CD13 Regulation of Endocytic Integrin Recycling	Poster	Gordon Conference	2016	New Hampshire
CD13 Regulation of Dendritic Cell Endocytosis	Poster	Keystone Symposia	2016	Killarney, Ireland
CD13 as a Vascular Regulator	Talk	University of Iowa	2016	Iowa City, IA
CD13 as a Vascular Regulator	Talk	Medical College of Georgia	2016	Augusta, GA
CD13 Regulation of Innate Immunity	Talk	American Association of Immunology	2015	New Orleans, LA
CD13 is a Novel Regulator of TLR4 Endocytosis in Dendritic Cells	Poster	Keystone Symposia	2013	Keystone, CO
Modulation of CD13 expression may enhance stem cell engraftment for tissue and organ repair	Poster	STEMConn	2013	New Haven, CT
Matrix and Biomechanical Signals	Lecture	Gordon Research Conference on Vascular Cell Biology	2013	Ventura, California
CD13 Normalizes Vasculature in Solid Tumors and Regulates Adherens Junctions	Poster	University of Connecticut Health Center Graduate Student Research Day	2013	Farmington, Connecticut
Department of Microbiology and Immunology Seminar Series	Talk	Nortwestern University	2013	Chicago, IL
Pediatric Research Seminar Series	Talk	Connecticut Children's Medical Center	2013	Farmington, CT
CD13 regulates immune cell trafficking to solid tumors	Talk	American Association of Immunologists National Research Conference	2012	Boston, MA
CD13 phosphorylation and cytoskeletal anchors in Monocyte adhesion	Poster	North American Vascular Biology Organization	2012	Hyannis, MA
CD13 regulates dendritic cell cross-presentation and t cell responses by inhibiting receptor-mediated antigen uptake	Talk	American Association of Immunologists Annual Meeting	2012	Boston, MA
Modulation of CD13 expression may enhance stem cell engraftment for tissue and organ repair	Poster	New York Stem Cell Foundation	2012	New York, NY
CD13 is involved in immune cell trafficking in inflammation and solid tumors	Poster	North American Vascular Biology Organization	2011	Hyannis, MA
Trafficking and functional roles of myeloid cells lacking CD13 in inflammatory diseases	Poster	Gordon Conference	2011	Newport, RI
CD13 Regulates Mesenchymal Stem Cell Function	Poster	North American Vascular Biology Organization (NAVBO) Research Conference	2011
Special Seminar	Talk	Institute of Medical Biology/Biochemistry, Ernst-Moritz-Arndt University	2011	Greifswald, Germany
Kentucky Pediatric Research Institute Seminar	Talk	University of Kentucky	2008	Lexington, KY
Vascular Biology Seminar Series	Talk	Yale University Medical School	2005	New Haven, CT
Keynote Speaker	Talk	4th St. Gerlach Vascular Biology Congress	2002	St. Gerlach, Netherlands
Vascular Biology Seminar Series	Talk	Dartmouth Medical School	2002	Hanover, NH
Center for Vascular Biology Seminar Series	Talk	University of Connecticut Medical School	2001	Farmington, CT
Conference on Cell Surface Peptidases	Talk	Danish Society for Biochemistry and Molecular Biology	2001	Copenhagen, Denmark