Update Your ProfileAcademic Title:
Professor
Primary Appointment:
Surgery
Secondary Appointment(s):
Physiology
Administrative Title:
Director, Center for Vascular & Inflammatory Diseases
Location:
UMB BioPark Room 219
Phone (Primary):
410-706-8010
Education and Training
Undergraduate Degree: B.S. Chemistry, Southern Nazarene University, 1973
Graduate Degree: Ph.D. Biochemistry, University of Kansas, 1978
Postdoctoral Fellowship: University of Notre Dame, 1978 - 1981
Biosketch
Dr. Strickland's laboratory was one of two laboratories to identify the LDL receptor related protein (LRP1) as an hepatic receptor involved in the removal of protease-inhibitor complexes (a2M-protease or serpin-protease). While identifying LRP1, the Strickland laboratory also discovered the 39 kDa Receptor Associated Protein (RAP), a molecular chaperone for this receptor family. We now know that LRP1 is an efficient endocytic and signaling receptor that is widely expressed in the vasculature, in neurons and in inflammatory cells such as macrophages. Ongoing projects in the Strickland laboratory include investigating the role of LRP1 in regulating thrombosis, cell migration, proliferation and signaling events, ultimately altering the pathology of certain diseases such as vascular remodeling, atherosclerosis, and vessel wall pathology.
Research/Clinical Keywords
Lipoprotein receptors, vascular disease, thrombosis, atherosclerosis, aneurysms, Alzheimer's disease
Highlighted Publications
Ashcom, J.D., Tiller, S.E., Dickerson, K., Cravens, J.L., Argraves, S.W., and Strickland, D.K. (1990) The Human a2-macroglobulin receptor: Identification of a 420 kda cell surface glycoprotein specific for the proteolyzed conformation of a2-macroglobulin. J. Cell Biol., 110, 1041-1048
Strickland, D.K., Ashcom, J.D., Williams, S., Burgess, W.H., Migliorini, M., and Argraves, W.S. (1990) Sequence identity between the a2-macroglobulin receptor and low density lipoprotein receptor-related protein suggests that this molecule is a multifunctional receptor. J. Biol. Chem., 265, 704-17404.
Herz, J., Goldstein, J.L., Strickland, D.K., Ho, Y.K., and Brown, M.S. (1991) 39 kDa protein modulates binding of ligand to low density lipoprotein-related protein/2-macroglobulin receptor. J. Biol. Chem., 266, 21232-21238
Lee, D., Walsh, J.D., Mikhailenko, I., Yu, P., Migliorini, M., Wu, Y. Krueger,S., Curtis, J.E., Harris, B., Lockett, S., Strickland, D.K*., and Wang, Y-X*. (2006) The Receptor Associated Protein Uses a Histidine Switch to Modulate its Interaction with the LDL Receptor Related Protein (LRP) in the ER and Golgi Molecular Cell 22, 423-430 (*corresponding authors)
Kounnas, M.Z., Moir, R.D., Rebeck, G.W., Bush, A.I., Argraves, W.S., Tanzi, R.E., Hyman, B.T., and Strickland, D.K. (1995) LDL recetor related protein, a multifunctional apoE receptor, binds secreted -amyloid precursor protein and mediates its degradation. Cell, 82, 331-340
Muratoglu, SC, Belgrave, S., Hampton, B., Migkiorini, M., Clksaygan, T., Chen, L., Mikhailenko, I and Strickland, DK. (2013). LRP1 protects the vasculature by regulating levels of Connective Tissue Growth Factor and HtrA1. Arterioscler Thromb Vas Biol 33:2137-46
Prasad, J.M., Young, P.A. and Strickland, D.K. (2016) High affinity binding of the receptor-associated protein D1D2 domains with LRP1 involves bivalent complex formaiton: Critical roles of lysines 60 and 191. J. Biol. Chem., 291, 18430-9
Awards and Affiliations
1973 Individual NIH Postdoctoral Fellowship
1988 - 1993 Research Career Development Award, NHLBI, National Institutes of Health
1993 - 1997 Member, Hematology II Study Section, NIH;
1994 Tiffany Award for Technical Excellence, American Red Cross;
1993 Plenary Lecturer, International Congress on Fibrinolysis;
1996 Distinguished Researcher Award, GeorgeWashingtonUniversity;
2003 Invited speaker EMBO conference on “Extracellular Proteases and their Inhibitors in Development, Plasticity and Pathology of the Nervous system” Ascona, Switzerland
2003 Invited State-of-the-art lecture, International Congress of Hemostasis and Thrombolysis.
2004 Invited Speaker, Plasminogen activation and Extracellular Proteolysis Gordon Conference;
2005 Invited State-of-the art lecture, International Congress of Hemostasis and Thrombosis (Sydney);
2008 Invited Speaker, Proteases and their Inhibitors Gordon Conference,
2005-2009 AHA National Thrombosis Study Section
2010 Plasminogen Activation and Extracellular Proteolysis Gordon Conference, Invited Speaker
2009-2013 MidAtlantic American Heart Association Advisory Council
2010-2013 Chair, MidAtlantic American Heart Association Advisory Council
2009-2011 Member, Hemostasis and Thrombosis Study Section (NIH)
2011-2013 Chair, Hemostasis and Thrombosis Study Section (NIH)
2012 Sol Sherry Distinguised Lecture in Thrombosis (American Heart Association)
2012 Plasminogen Activation and Extracellular Proteolysis Gordon Conference, Invited Speaker
2013 Invited speaker, ApoE and Alzheimer’s disease symposium, Georgetown University
2014 Faculty Award for Diversity and Inclusion Award, University of Maryland School of Medicine
2016 Invited State-of-the-art lecture, International Soceity of Fibrinolysis and Proteolysis
Grants and Contracts
R01 HL114379-01
Role of lipoprotein receptors in venous thrombosis
The major goals of this project are to test the hypotheses 1) that the LDLr modulates thrombus resolution during DVT by modulating inflammation; 2) that LRP1 modulate thrombus resolution by regulating protease levels and by regulating signaling events in inflammation and 3) that we can engineer inhibitor molecules for receptor blockade that would enhance thrombus resolution in DVT.
R01 HL1120388
Mechanism by which LRP1 protects the vasculature
The objectives of this grant are to test the hypothesis LRP1 maintains the integrity of the vessel wall by: 1) modulating protease activity which prevents elastin degradation and 2) by regulating the non-cannonical TGFb signaling pathway thereby affecting SMC physiology. Further, the hypothesis that rare LRP1 variants contribute to aneurysm formation in humans will be tested.
Marfan Foundation
Role of LRP1 in Marfan's syndrome
The objectives of this grant are to test the hypothesis that that LRP1 cross-talks with angiotensin II type 1 receptor (AT1r) to modulate signaling pathways that are key for extracellular matrix development and homeostasis in the vasculature.
T32 HL007698-18
Interdisciplinary Training Program in Cardiovascular Disease
The objectives of this training program are to provide training for five predoctoral and five postdoctoral trainees in basic and translational sciences as they apply to cardiovascular medicine.