Sergey L. Leikin, Ph.D.
Section on Physical Biochemistry
The extracellular matrix (ECM) is involved in a wide variety of disorders, ranging from rare genetic abnormalities of skeletal development to such common ailments as osteoporosis, fibrosis, and cancer. Our interest in ECM biology began with studies on basic principles relating the structure of collagen and DNA to their interactions and biological function. Over the years, the focus of our research shifted to collagens, which are the most abundant ECM molecules, and then to ECM disorders and the development of novel treatments for these disorders. We gradually phased out DNA studies and concentrated on ECM pathology in cancer, fibrosis, osteogenesis imperfecta (OI), Ehlers-Danlos syndrome (EDS), chondrodysplasias, osteoporosis, and other diseases. We utilize diverse approaches of molecular and cell biology, physics, chemistry, and biochemistry to investigate how mutations affect collagen folding, trafficking, processing, intracellular degradation, secretion, and ECM function. We are also developing new imaging approaches and methods for these studies, e.g., high definition infrared and Raman technologies. Our goal is to understand molecular mechanisms and treatment targets in ECM disorders and bring this knowledge to clinical research and practice.
Dr. Sergey Leikin obtained his M.S. in Physics in 1984 under Prof. Abrikosov, a 2003 Nobel Laureate in Physics, from the Moscow Steel and Alloys Institute, Russia. He received his Ph.D. in Biophysics in 1987 from the Moscow State University, Russia and completed his postdoctoral training with Dr. Adrian Parsegian in 1992, at the Division of Computer Research and Technology (DCRT), NIH, in which he remained as a tenure-track investigator. His lab moved from DCRT to NICHD in 1997. He has headed the Section on Physical Biochemistry since 2002.
Omari S, Makareeva E, Roberts-Pilgrim A, Mirigian L, Jarnik M, Ott C, Lippincott-Schwartz J, Leikin S. Noncanonical autophagy at ER exit sites regulates procollagen turnover. Proc Natl Acad Sci U S A. 2018;115(43):E10099-E10108.
Mirigian LS, Makareeva E, Mertz EL, Omari S, Roberts-Pilgrim AM, Oestreich AK, Phillips CL, Leikin S. Osteoblast Malfunction Caused by Cell Stress Response to Procollagen Misfolding in α2(I)-G610C Mouse Model of Osteogenesis Imperfecta. J Bone Miner Res. 2016;31(8):1608-1616.
Makareeva E, Aviles NA, Leikin S. Chaperoning osteogenesis: new protein-folding disease paradigms. Trends Cell Biol. 2011;21(3):168-76.
Makareeva E, Cabral WA, Marini JC, Leikin S. Molecular mechanism of alpha 1(I)-osteogenesis imperfecta/Ehlers-Danlos syndrome: unfolding of an N-anchor domain at the N-terminal end of the type I collagen triple helix. J Biol Chem. 2006;281(10):6463-70.
Leikina E, Mertts MV, Kuznetsova N, Leikin S. Type I collagen is thermally unstable at body temperature. Proc Natl Acad Sci U S A. 2002;99(3):1314-8.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
Biomedical Engineering and Biophysics
This page was last updated on November 1st, 2019