Dr. Richard J. Kulmacz

Regular Member

The University of Texas Health Science Center at Houston
Medical School
Department of Internal Medicine

Research Interests:

• Structure, function and regulation of prostanoid biosynthetic enzymes and of cytochrome b561 family members.

The general goal of my lab is to characterize the mechanisms, regulation, and pharmacology of two distinct groups of membrane proteins: prostanoid biosynthetic enzymes and cytochrome b561 family members. One current focus is on prostaglandin H synthase-2, an enzyme with important roles in inflammation, carcinogenesis, wound healing, and reproductive function. This enzyme is regulated by reactive oxygen species, and it is the target of an exciting new class of non-steroidal anti-inflammatory (and potentially anti-carcinogenic) drugs. Our second current focus is on adrenal cytochrome b561, which is required for biosynthesis of catecholamine neurotransmitters, and on other members of the cytochrome b561 family whose functions are being investigated.  Our general approach is to use biochemical and biophysical characterization of native proteins and specific mutants to study the relationship between protein structure and catalytic function.

A tutorial rotation in the lab offers the opportunity to use a variety of molecular, biochemical, spectroscopic, and kinetic techniques to better understand the ways the structure of these proteins influences their participation in health and disease processes.

Selected Publications:

Doyen JR, Yucer N, Lichtenberger LM, Kulmacz RJ (2008) Prostaglandins Other Lipid Mediat 85, 134-143.Phospholipid actions on PGHS-1 and -2 cyclooxygenase kinetics.

Liu W, Rogge CE, da Silva GFZ, Shinkarev VP, Tsai AL, Kamensky Y, Palmer G, Kulmacz RJ (2008) Biochim Biophys Acta 1777, 1218-1228. His92 and His110 Selectively Affect Different Heme Centers of Adrenal Cytochrome b561.

Rogge CE, Liu W, Kulmacz RJ, Tsai AL (2009) J Inorg Biochem 103, 912-922. Peroxide-induced radical formation at Tyr385 and Tyr504 in human PGHS-1.

Wu G, Tsai AL, Kulmacz RJ (2009) Biochemistry 48, 11902-11911. Cyclooxygenase competitive inhibitors alter tyrosyl radical dynamics in prostaglandin H synthase-2.

Tsai AL, Kulmacz RJ (2010) Arch Biochem Biophys 493, 103-124. Prostaglandin H synthase: resolved and unresolved mechanistic issues.

Liu W, Poole EM, Ulrich CM, Kulmacz RJ (2010) Pharmacogenomics J, in press.  Polymorphic human prostaglandin H synthase-2 proteins and their interactions with cyclooxygenase substrates and inhibitors.

Additional Publications

Program Affiliations:

Program in Biochemistry and Molecular Biology