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Anastasia Kralli, Ph.D.

Associate Professor Adjunct
Department of Molecular Medicine
California Campus
Laboratory Website
Scripps VIVO Scientific Profile
kralli@scripps.edu
(858) 784-7287

Scripps Research Joint Appointments

Department of Cell and Molecular Biology

Research Focus

Organisms go through cycles of metabolic activity, driven by internal cues (circadian, circannual clocks) and physiologic/behavioral inputs (e.g. feeding/fasting, physical activity/rest). In addition, organisms face environmental challenges (physical, chemical or psychological stressors) that require continual adaptation of the pathways regulating metabolism. The goal of our research is to elucidate the regulatory and transcriptional mechanisms that integrate information and enable physiologic adaptations (particularly in response to changes in physical activity, environmental temperature, nutritional state), and that, when deregulated, contribute to metabolic disease.

Our studies focus on the Estrogen-Related Receptors (ERRα, ERRβ, and ERRγ), which we use as an entry point to the study of the regulatory / transcriptional networks that are important for adaptation in adipose tissue and in skeletal muscle, in response to changes in environmental temperature, physical exercise and/or diet. In past studies, we have shown that ERRs, and in particular ERRα, co-ordinate gene expression programs that regulate mitochondrial biogenesis and oxidative capacity. Our current studies build on this past work, using mouse models with genetically modified loci for ERRs (floxed alleles) and dissecting the unique and shared roles of ERRs in adipose tissue and in skeletal muscle. We are also identifying novel mechanisms that regulate ERR activity, as well as new important downstream effectors of ERRs, thereby expanding the network of regulators of mitochondrial oxidative function. Our studies identify and probe new avenues for therapeutic intervention in states where oxidative metabolism and tissue function are compromised, such as insulin resistance and type 2 diabetes, disease-associated muscle atrophies and age-related degenerative diseases.

Education

B.S., Biology, University of Sussex, 1986
Ph.D., Molecular Biology, University of Pennsylvania, 1991

Professional Experience

1987 - 1991 Ph.D. thesis with Dr. R. Weinmann, University of Pennsylvania / Wistar Institute, Philadelphia, PA
1991 - 1997 Postdoctoral fellow with Dr. K. R. Yamamoto, University of California, San Francisco, CA
1997 - 2003 Junior group leader, Division of Biochemistry, Biozentrum of the Univ. of Basel, Switzerland
2003 - 2006 Assistant Professor, Department of Cell Biology, The Scripps Research Institute, CA

Awards & Professional Activities

Selected References

All Publications

Cho Y., Hazen B.C., Gandra P.G., Ward S.R., Schenk S., Russell A.P. and A. Kralli (2015). Perm1 enhances mitochondrial biogenesis, oxidative capacity and fatigue resistance in adult skeletal muscle. FASEB J. fj.15-276360, in press.

Gantner M.L., Hazen B.C., Conkright J. and A. Kralli (2014). GADD45gamma regulates the thermogenic capacity of brown adipose tissue. Proc. Natl. Acad. Sci. U S A. 111, 11870-11875.

Cho Y., Hazen B.C., Russell A.P. and A. Kralli (2013). PGC-1 and ERR-induced Regulator in Muscle 1 (PERM1) is a tissue-specific regulator of oxidative capacity in skeletal muscle cells. J. Biol. Chem. 288, 25207-18.

Enguix N., Pardo R., González A., Simó R., Kralli A. and J. A. Villena (2013). Mice lacking PGC-1β in adipose tissue reveal a dissociation between mitochondrial dysfunction and insulin resistance. Mol. Metab. 2, 215-26.

Gan Z., Rumsey J., Hazen B.C., Lai L., Leone T.C., Vega R.B., Xie H., Conley K.E., Auwerx J., Smith S.R., Olson E.N., Kralli A. and D.P. Kelly (2013). Nuclear Receptor-microRNA Circuitry Links Muscle Fiber Type to Energy Metabolism. J. Clin. Invest. 123, 2564-2575.

Hock M.B. and A. Kralli (2009). Transcriptional Control of Mitochondrial Biogenesis and Function. Annu. Rev. Physiol. 71, 177-203.