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Olivier Kocher, MD, PhD

Associate Professor of Pathology
Beth Israel Deaconess Medical Center
Harvard Medical School

330 Brookline Avenue, RN 270C
Boston, MA 02215

Office: 617-667-3598
Fax: 617-667-3591
Email: okocher@bidmc.harvard.edu

Kocher Lab >>

Education/Training/Appointments

1981, MD, Univ. of Geneva Medical School, Geneva, Switzerland; 1987, PhD, Univ. of Geneva, Faculty of Sciences (Biology), Geneva, Switzerland; 1987-1989, Post-doctoral fellow (Pathology) (Laboratory of Dr.J.A. Madri, Department of Pathology, Yale University, New Haven, Connecticut; 1989-1992, Residency (Pathology), Beth Israel Hospital, Boston, MA; 1992-present: Staff pathologist and researcher in the Department of Pathology at BIDMC.

Research Interests

  • Atherosclerosis
  • Cholesterol Metabolism
  • PDZK1

Basic Research

Adaptor, anchoring and scaffolding proteins play an important role in signal transduction. In many situations, the interaction between signaling proteins is mediated by small amino acid sequences binding to specific proteins domains, such as src homology (SH), pTyr-binding (PTB) or PDZ domains. These interactions are responsible for determining location, function and activity of receptors and transporter proteins among others. A few years ago, we isolated a novel protein that we named PDZK1. PDZK1, contains four PDZ protein-interactions domains and interacts with the carboxy-terminal portion of a number of membrane associated proteins including cMOAT (MRP2) the canalicular multispecific organic anion transporter associated with multidrug resistance, the cystic fibrosis transmembrane conductance regulator CFTR, the chloride channel CLC-3B, the type lla Na/Pi cotransporter, the Na-H exchanger NHE3, the chloride-anion exchanger CFEX and the high density lipoprotein (HDL) scavenger receptor SR-BI. These new findings define PDZK1 as a major player in the organization of membrane associated proteins including cell surface receptors and ion transporters. As a result, PDZK1 is likely to play an important role in biological processes as diverse as lipid metabolism and cardiovascular disease, ion channel organization and multidrug resistance.

We generated a PDZK1 knockout mouse which is characterized by increased plasma cholesterol levels and markedly reduced expression of SR-BI in the liver, resulting in impaired "reverse cholesterol transport". PDZK1 joins ARH (the product of the defective gene in autosomal recessive hypercholesterolemia) in what is likely to be a growing family of cytoplasmic adaptor proteins that control the tissue specific activity of cell surface receptors.

Our goals are: 1) to study the nature of the interaction between PDZK1 and SR-BI in the liver and understand the role played by PDZK1 in optimizing reverse cholesterol transport, 2) to determine if a functional PDZK1 gene is protective against the development of atherosclerosis 3) to identify the putative molecule that plays the role of PDZK1 in the organization of SR-BI in steroidogenic organs.

New and Noteworthy Publications

View all publications via PubMed >>

  1. Kocher O, Pal R, Roberts M, Cirovic C and Gilchrist A. Targeted disruption of the PDZK1 gene by homologous recombination. Molecular and Cellular Biology, 2003, 23:1175-1180.

  2. Kocher O, Yesilaltay A, Cirovic C, Pal R, Rigotti A and Krieger M. Targeted disruption of the PDZK1 gene in mice causes tissue-specific depletion of the HDL receptor SR-BI and altered lipoprotein metabolism. J. Biol. Chem. 2003, 278:52820-52825.

  3. Yesilaltay A, Kocher O, Pal R, Leiva A, Quiñones V, Rigotti A, and Krieger M. PDZK1 is required for maintaining hepatic SR-BI's steady state levels but not its surface localization or function. J. Biol. Chem. 2006, 281:28975-28980.

  4. Yesilaltay A, Kocher O, Rigotti A and Krieger M. Regulation of SR-BI-mediated high density lipoprotein metabolism by the tissue specific adaptor protein PDZK1. Curr Opin Lipidol, 16:147-152, 2005.

  5. Kocher O, Yesilaltay A, Shen C, Zhang S, Daniels K, Pal R, Chen J and Krieger M. Influence of PDZK1 on Lipoprotein Metabolism and Atherosclerosis. Biochim Biophys Acta., 2008, in press.

Contact Information

Nicole Magner, Administrative Assistant
Center for Vascular Biology Research
Beth Israel Deaconess Medical Center
Research North
99 Brookline Avenue
Boston, MA 02215
617-667-0654
info.cvbr@bidmc.harvard.edu