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David Lombard, M.D., Ph.D.

Title and department:
Assistant Research Professor, Institute of Gerontology
Assistant Professor, Pathology

Mailing address:
University of Michigan
3015 BSRB
109 Zina Pitcher Place
Ann Arbor, MI 48109-2200

Lab address:
University of Michigan
3118, 3128 BSRB
109 Zina Pitcher Place
Ann Arbor, MI 48109-2200

Phone: (734) 615-0498; Fax: (734) 936-9220

E-mail: davidlom@umich.edu

Links to laboratory or personal web pages:
http://www.pathology.med.umich.edu/faculty/Lombard/index.html

Research Interests
Aging is a conserved but poorly understood biological phenomenon. In invertebrates, overexpression or hyperactivity of sirtuins – homologs of the yeast Sir2 deacetylase – confer extended lifespan. Mammals possess seven sirtuins, called SIRT1-SIRT7. Many of these proteins modulate metabolic processes; their potential roles in regulating aging in mammals are uncharacterized. We previously showed that SIRT3 is a mitochondrial factor that deacetylates numerous protein targets in this organelle; we are currently elucidating the biological significance of this activity. More recently we have found that calorie restriction (CR), an intervention that extends lifespan in many organisms, is also associated with perturbations in mitochondrial acetylation. We are currently working to understand the impact of CR-related acetylation changes on one key substrate identified in these studies, the pyruvate dehydrogenase complex (PDC). PDC governs metabolic flux into the Krebs cycle and is the major regulator of glucose utilization in mammals.

With respect to non-mitochondrial sirtuins, we previously showed that SIRT6 is a nuclear protein that suppresses genomic instability and enhances genotoxin resistance in cells. SIRT6-deficient mice die of a degenerative disorder characterized by profound metabolic abnormalities. We are working to understand the basis for this phenotype through cell culture studies as well as analysis of conditional knockouts and overexpressing mouse models.

Brief Biography
Dr. Lombard received a Ph.D. in Biology from Massachusetts Institute of Technology (2000) and an M.D. from Harvard Medical School (2001). He completed residency training in Anatomic Pathology (2001-2003) at Brigham and Women's Hospital in Boston. Following residency training Dr. Lombard joined the laboratory of Professor Frederick Alt at Children's Hospital as a postdoctoral fellow. In 2008, Dr. Lombard joined the faculty of the University of Michigan as an assistant professor in the Department of Pathology and holds a joint appointment in the Institute of Gerontology as research assistant professor.

Dr. Lombard has been designated a New Scholar in Aging by the Ellison Medical Foundation, and a Scholar in the Biological Sciences Scholars Program at University of Michigan. 
   
Recent Publications
Mostoslavsky R*, Chua KF*, Lombard DB*, Pang WW, Fischer MR, Gellon L, Liu P, Mostoslavsky G, Franco S, Murphy MM, Mills KD, Patel P, Hsu JT, Hong AL, Ford E, Cheng HL, Kennedy C, Nunez N, Bronson R, Frendewey D, Auerbach W, Valenzuela D, Karow M, Hottiger MO, Hursting S, Barrett JC, Guarente L, Mulligan R, Demple B, Yancopoulos GD, Alt FW. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6.  Cell. 2006;124(2):315-29.

Lombard DB,* Alt FW, Cheng H, Bunkenborg J, Streeper RS, Mostoslavsky R, Kim J, Yancopoulos G, Valenzuela D, Murphy A, Yang Y, Chen Y, Hirschey MD, Bronson RT, Haigis MC, Guarente LP, Farese R, Weissman S, Verdin E, Schwer B*. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. MCB. 2007;27(24):8807-14.

Lombard DB, Schwer B, Alt FW, Mostoslavsky R. SIRT6 in DNA repair, metabolism, and aging. J Intern Med. 2008;263(2):128-41.

Yang B, Zwaans BMM, Eckersdorff M, Lombard DB. The sirtuin SIRT6 deacetylates H3 K56Ac in vivo to promote genomic stability. Cell Cycle. 2009;8(16):2662-3.

Schwer B*, Eckersdorff M*, Li Y*, Silva JC, Kurtev MV, Comb MJ, Alt FW, Lombard DB*. Calorie restriction alters mitochondrial protein acetylation. Aging Cell. 2009;8(5):604-6.