Faculty and Staff
Nutritional and Metabolic Doctoral Training Faculty
Lawrence S. Shapiro, Ph.D.
Biochemistry & Molecular Biophysics
BA, 1988 New York University
MS, 1993 Columbia University
M.Phil, Columbia University
Ph.D., 1996 Columbia University
The work of the Shapiro lab is focused on the protein chemistry and structural biology of proteins involved in energy homeostasis. This work is now aimed at two primary areas, (1) the structural biology and function of adipocyte-secreted hormones, also called "adipokines", and (2) structure and function studies on proteins that coat the "lipid droplet" organelles of adipocytes. Dr. Shapiro's laboratory has determined high-resolution structures for two novel adipokines, adiponectin – a liver-specific insulin-sensitizer, and resistin – a hormone that decreases insulin sensitivity in the liver. Both adiponectin and resistin circulate in the blood in two different multimeric states. The structures of these proteins, in combination with physiological insulin clamp experiments, suggest novel mechanisms of action that are controlled, at least in part, by the multimeric state of each hormone. Several lines of research are underway to determine their mechanism of action in greater detail. Intracellular signaling for both of these hormones converge on the important regulator of energy homeostasis, the AMP-activated protein kinase (AMPK). Structural studies of AMPK are currently underway. The second major are of research in the Shapipro lab is focused on understanding the mechanism of fat storage in adipocytes, and the controlled lipolysis of these stores. Lipid droplets are organelles that are coated with a protein called perilipin. Perilipin, controls access to stored triglyceride both by blocking basal lipolysis and serving as a phosphorylation-activated docking site for hormone-sensitive lipase. Details of the mechanism of function of perilipin are not yet known, and Dr. Shapiro is pursuing structural studies to help understand this important protein.
Recent Publications - Pubmed
Dynamic properties of a type II cadherin adhesive domain: implications for the mechanism of strand-swapping of classical cadherins. Miloushev VZ, Bahna F, Ciatto C, Ahlsen G, Honig B, Shapiro L, Palmer AG 3rd., Structure, 6;16(8):1195-205 (2008).
Sequence and structural determinants of strand swapping in cadherin domains: do all cadherins bind through the same adhesive interface? Posy S, Shapiro L, Honig B., J Mol Biol., 378(4):954-68 (2008).
Crystal structures of beta-neurexin 1 and beta-neurexin 2 ectodomains and dynamics of splice insertion sequence 4. Koehnke J, Jin X, Trbovic N, Katsamba PS, Brasch J, Ahlsen G, Scheiffele P, Honig B, Palmer AG 3rd, Shapiro L., Structure,. 16(3):410-21 (2008)