Shekhar Kumar, PhD
Research Assistant Professor of Pediatrics (Hematology)
Department: Pediatrics
Contact information
Children’s Hospital of Philadelphia
310 C Abramson Research Building
3615 Civic Center Blvd.
Philadelphia, PA 19104
310 C Abramson Research Building
3615 Civic Center Blvd.
Philadelphia, PA 19104
Office: 215-590-0333
Email:
kumars@email.chop.edu
kumars@email.chop.edu
Education:
BS (Biotechnology)
Patna University, Patna, India, 2000.
MS (Biotechnology)
All India Institute of Medical Sciences, New Delhi, India, 2003.
PhD (Biochemistry)
Jawaharlal Nehru University, New Delhi, India, 2010.
Permanent linkBS (Biotechnology)
Patna University, Patna, India, 2000.
MS (Biotechnology)
All India Institute of Medical Sciences, New Delhi, India, 2003.
PhD (Biochemistry)
Jawaharlal Nehru University, New Delhi, India, 2010.
Description of Research Expertise
Our laboratory investigates the molecular mechanisms of blood clot formation with the goal of developing knowledge-based strategies to prevent excessive clotting or bleeding.We use tools of biochemistry and structural biophysics to explore how macromolecular interactions involved in the assembly of the coagulation complexes modulates enzyme’s function, and how deviation from the normal function leads to bleeding or thrombosis.
In this effort we are combining concepts and approaches from structural biology and biochemistry to investigate the complex interplay of clotting factors in the blood coagulation process. Our repertoire of structural approaches includes x-ray crystallography, small angle x-ray scattering, hydrogen-deuterium exchange, and single molecule reconstruction by cryo-electron microscopy. These complementary capabilities bring an innovative approach to the field of coagulation biology.
Keywords: blood coagulation, coagulation factor, serine protease, proteolytic enzymes, thrombosis, factor V/Va, thrombin, factor X/Xa, factor VIII/VIIIa, prothrombinase, tenase
Selected Publications
Haixiang Yu, Shekhar Kumar, James W. Frederiksen, Vladimir N. Kolyadko, George Pitoc, Juliana Layzer, Amy Yan, Rachel Rempel, Samuel Francis, Sriram Krishnaswamy & Bruce A. Sullenger : Aptameric hirudins as selective and reversible EXosite-ACTive site (EXACT) inhibitors. Nature Communications volume 15, Article number: 3977 (2024) 2024.Shekhar Kumar, Sriram Krishnaswamy: Design of a Superior Factor VIIIa Mimetic By Coupling a Membrane Binding Domain to a Factor IXa Binding Antibody Fragment. Blood (2023) 142 (Supplement 1): 22. Blood 142 (Supplement 1), 2023.
Shekhar Kumar, Haixiang Yu, Bruce A. Sullenger, Sriram Krishnaswamy: X-Ray Structures of Thrombin Bound to Heterobifunctional Aptamer-Drug Conjugates Reveal the Mechanistic Basis for a Novel Tethered Inhibition Strategy. International Society on Thrombosis and Haemostasis Annual Meeting, 2023, Montreal, CA 2023.
Shekhar Kumar, Haixiang Yu, Bruce A. Sullenger, Sriram Krishnaswamy: X-Ray Structure of Thrombin Bound to a Heterobifunctional Aptamer-Drug Conjugate Reveals the Mechanistic Basis for a Novel Tethered Inhibition Strategy. Blood (2022) 140 (Supplement 1): 1668–1669. 2022.
Soule EE, Yu H, Olson L, Naqvi I, Kumar S, Krishnaswamy S, Sullenger BA.: Generation of an anticoagulant aptamer that targets factor V/Va and disrupts the FVa-membrane interaction in normal and COVID-19 patient samples. Cell Chem Biol 29: 215-225, 2022.
Vandna Sharma, Shekhar Kumar, Girish Sahni: Kringles of substrate plasminogen provide a “catalytic switch” in plasminogen to plasmin turnover by Streptokinase. Biochemical Journal 477 (5): 953–970, 2020.
Gunaratne, R*., Kumar, S*., Frederiksen, J.W., Stayrook, S., Lohrmann, J.L., Perry, K., Bompiani, K.M., Chabada, C.V., Thalji, N.K., Ho, M.D., Arepally, G., Camire, R.M., Krishnaswamy, K., and Sullenger, B.A: Combination of aptamer and drug for reversible anticoagulation in cardiopulmonary bypass. Nature Biotechnology 36(7): 606-613, 2018 Notes: * Co-first author, Featured as Paper of the Month by Oligonucleotide Therapeutics Society.
Pooja Sawhney, Shekhar Kumar, Neeraj Maheshwari, Sumeet Singh Guleria, Neelam Dhar, Radhika Kashyup, Girish Sahni: Site-Specific Thiol-mediated PEGylation of Streptokinase Leads to Improved Properties with Clinical Potential. Current Pharmaceutical Design 22(38): 5868-5878, 2016.
S Kumar, S Krishnaswamy: Thrombin Formation In: Gonzalez E., Moore H., Moore E. (eds) Trauma Induced Coagulopathy. Springer, Cham Page: 55-74, 2016.
S Kumar, W Deng, S Stayrook, R Li, RM Camire, S Krishnaswamy: Structural Basis for the Procofactor to Cofactor Transition in Human Factor V American Society of Hematology Annual Meeting, San Diego, 2016, Blood (2016) 128 (22), 253-253. (Oral presentation) 2016.