User:Lawrence Kazak

Lawrence Kazak, PhD
Post-doctoral fellow
Department of Cancer Biology and Division of Metabolism and Chronic Disease, Dana-Farber Cancer Institute
Department of Cell Biology, Harvard Medical School
Laboratory of Dr. Bruce M. Spiegelman
Boston, MA, USA, 02215
email: Lawrence_Kazak@dfci.harvard.edu

Current Appointment

• 2013-present, Postdoctoral Fellow, Division of Metabolism and Chronic Disease, Dana-Farber Cancer Institute, Department of Cell Biology, Harvard Medical School, Boston, MA Dr. Bruce M. Spiegelman

Education

• 2008-2013, PhD, Biological Science, University of Cambridge, Cambridge, UK Dr. Ian J. Holt
• 2005-2008, MSc, Kinesiology and Health Science, York University, Toronto, Canada. Supervisor: David A. Hood
• 2001-2005, BA, York University, Toronto, Canada

Funding

current
2017-2022: K99/R00, NIH Pathway to Independence Award
past
2014-2017: Canadian Institutes of Health Research postdoctoral fellowship [1].
2008-2011: Cambridge Commonwealth Trust
2008-2011: Overseas Research Trust

Research

current
I am currently a Post-doctoral Fellow at the Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School. I work in the lab of Dr. Bruce M. Spiegelman. I am investigating the regulation of adaptive thermogenesis by adipose tissue, using a combination of approaches including cell biology, biochemistry, genetics, quantitative proteomics, and bioenergetics. My scientific aims are centered around the identification of mechanisms that regulate adipose tissue energy expenditure. My future research will continue to focus on energy homeostasis in mammals. The primary emphasis will be directed towards understanding the relationship between mitochondrial function and the metabolic demand placed on the host in response to genetic and environmental perturbations.
past
I originally trained in the area of exercise and skeletal muscle physiology during my undergraduate and MSc degrees. My PhD was carried out at the University of Cambridge in the MRC Mitochondrial Biology Unit, under the supervision of Dr. Ian J. Holt. Over the course of my PhD, I used the tools of molecular biology, genetics, and biochemistry to understand the mechanisms that regulate mammalian mitochondrial DNA replication and the targeting of proteins to mitochondria via alternative translation initiation.

Research interests

1. Energy Metabolism
2. Mitochondrial Biology
3. Adipogenesis
4. Genetics
5. Exercise Physiology

Ad hoc reveiwer

1. Nucleic Acids Research
2. PLOS ONE
3. Journal of Clinical Investigation
4. Scientific Reports
5. Skeletal Muscle
6. Pharmaceuticals

Selected Publications

1. Kazak L, Chouchani ET, Stavrovskaya IG, Lu GZ, Jedrychowski MP, Egan DF, Kumari M, Kong X, Erickson BK, Szypt J, Rosen ED, Murphy MP, Kristal BS, Gygi SP, and Spiegelman BM. (2017). UCP1 deficiency causes brown fat respiratory chain depletion and sensitizes mitochondria to calcium overload-induced dysfunction. PNAS. Epub ahead of print. 2. Bertholet AM, Kazak L, Chouchani ET, Bogaczynska MG, Paranjpe I, Wainwright GL, Betourne A, Kajimura S, Spiegelman BM, and Kirichok Y. (2017). Mitochondrial Patch-Clamp of Beige Adipocytes Reveals UCP1-positive and UCP1-negative Cells Both Exhibiting Futile Creatine Cycling. Cell Metabolism. Apr 4;25(4):811-22. 3. Kumari M, Wang X, Lantier L, Lyubetskaya A, Eguchi J, Kang S, Tenen D, Roh HC, Kong X, Kazak L, Ahmad R, and Rosen ED. IRF3 promotes adipose inflammation and insulin resistance and represses browning. JCI. 2016. [2] 4. Chouchani ET*, Kazak L*, Jedrychowski MP, Lu GZ, Erickson BK, Szpyt J, Pierce KA, Laznik-Bogoslavski D, Vetrivelan R, Clish CB, Robinson AJ, Gygi SP, and Spiegelman BM. Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1. Nature. Apr 7;532(7597):112-6. 2016. [3] (* Co-first author) 5. Kazak L, Chouchani ET, Jedrychowski MP, Erickson BK, Shinoda K, Cohen P, Vetrivelan R, Lu GZ, Laznik-Bogoslavski D, Hasenfuss SC, Kajimura S, Gygi SP, and Spiegelman BM. A Creatine-Driven Substrate Cycle Enhances Energy Expenditure and Thermogenesis in Beige Fat. Cell. Oct 22;163(3):643-655. 2015. [4] 6. Kir S, White JP, Kleiner S, Kazak L, Cohen P, Baracos VE, and Spiegelman BM. Tumor-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature. Sep 4;513(7516):100-4. 2014. [5] 7. Kong X, Banks A, Liu T, Kazak L, Rao RR, Cohen P, Wang X, Yu S, Lo JC, Tseng YH, Cypess AM, Xue R, Kleiner S, Kang S, Spiegelman BM, and Rosen ED. IRF4 Is a Key Thermogenic Transcriptional Partner of PGC-1α. Cell. Jul 3;158(1):69-83. 2014. [6] 8. Ye L, Wu J, Cohen P, Kazak L, Khandekar MJ, Jedrychowski MP, Zeng X, Gygi SP, and Spiegelman BM. Fat cells directly sense temperature to activate thermogenesis. PNAS. Jul 23;110(30):12480-5. 2013. [7] 9. Kazak L, Reyes A, He J, Brea-Calvo G, Wood SR, Holen TT, and Holt IJ. A cryptic targeting signal creates a mitochondrial FEN1 isoform with tailed R-loop binding properties. Plos One. 8(5):e62340. 2013. [8] 10. Reyes A, Kazak L, Wood SR, Yasukawa T, Jacbos HT, and Holt IJ. Mitochondrial DNA Replication Proceeds via a Bootlace Mechanism Involving the Incorporation of Processed Transcripts. Nucleic Acids Res. Jun;41(11):5837-50. 2013. [9] 11. Kazak L, Reyes A, Duncan A, Rorbach J, Wood SR, Brea-Calvo G, Gammage P, Robinson AJ, Minczuk M, and Holt IJ. Alternative translation initiation augments the human mitochondrial proteome. Nucleic Acids Res. 2013. Feb 1;41(4):2354-69. [10] 12. Kazak L, Reyes A, Holt IJ. Minimizing the damage: repair pathways keep mitochondrial DNA intact. Nat Rev Mol Cell Biol. 2012. Oct;13(10):659-71. [11] 13. He J, Cooper HM, Reyes A, Di Re M, Kazak L, Wood SR, Mao CC, Fearnley IM, Walker JE, Holt IJ. Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit. Nucleic Acids Res. 2012. Jul;40(13):6097-108. [12] 14. Reyes A, He J, Mao CC, Bailey LJ, Di Re M, Sembongi H, Kazak L, Dzionek K, Holmes JB, Cluett TJ, Harbour ME, Fearnley IM, Crouch RJ, Conti MA, Adelstein RS, Walker JE, Holt IJ. Actin and myosin contribute to mammalian mitochondrial DNA maintenance. Nucleic Acids Res. 2011. Jul;39(12):5098-108. [13]