Roberta Gottlieb
Roberta Gottlieb
 
Gottlieb Lab
Chengqun Huang, Hua Julie Yuan, Rick Sayen, Cynthia Perry Garza, Grant Madigan, Roberta Gottlieb
 
Mitophagy
Mitophagy


Roberta Gottlieb, M.D.

Research Professor
Frederick G. Henry Chair in Life Sciences
Professor


Education/Training

The Johns Hopkins University, Baltimore, MD; B.A. 1980; Natural Science
The Johns Hopkins University, Baltimore, MD; M.D. 1984; Medicine




Positions

1984-87 Residency in Pediatrics, University of Texas Health Science Center, Houston, TX

1987-90 Fellowship in Pediatric Hematology/Oncology, U.T. M.D. Anderson Cancer Center, Houston, TX
Preceptor: William J. Lennarz, Department of Biochemistry and Molecular Biology, Co-preceptor: Eugenie S. Kleinerman, M.D., Department of Cell Biology

1990-92 Postdoctoral Fellowship, University of California San Diego School of Medicine, San Diego, CA
Preceptor: Michael Karin, Ph.D., Department of Pharmacology

1993-94 Postdoctoral Fellowship, The Scripps Research Institute. Preceptor: Bernard M. Babior, M.D., Ph.D. Dept Molec. & Exp. Med., Co-preceptor: Robert L. Engler, ACOS Research, V.A. Med. Ctr, La Jolla, CA

1994-95 Senior Research Associate, Dept Molec. & Exp. Medicine, The Scripps Research Institute, La Jolla, CA

1994-99 Research Biochemist, Department of Veterans Affairs Medical Center, San Diego, CA

1995-96 Assistant Member, Dept Molec.& Exp. Medicine, The Scripps Research Institute, La Jolla, CA

1997-2003 Adjunct Assistant Professor, Department of Medicine, University of California San Diego, La Jolla, CA

2003-present Adjunct Associate Professor, Department of Medicine, University of California San Diego, La Jolla, CA

1996-2006 Associate Professor, Dept Molec. & Exp. Medicine, The Scripps Research Institute, La Jolla, CA

2007-present Professor of Biology and Director of the BioScience Center, San Diego State University, San Diego, CA; Frederick G. Henry Chair in the Life Sciences

2005-present President and Founder, Radical Therapeutix, Inc.



Board Certifications

American Board of Pediatrics, June 1988

American Board of Pediatric Hematology and Oncology, June 1990 (recertified June 1996)


Honors and Awards

1991-93 Physician Postdoctoral Fellowship, Howard Hughes Medical Institute

1994-95 Minority Scientist Development Award, American Heart Association

1997 American Society of Hematology Junior Faculty Scholar Award

1997 Pew Scholar's Program in the Biomedical Sciences

2001 Fellow of the American Heart Association



Selected Peer-Reviewed Publications

  1. Whittaker R, Glassy MS, Gude N, Sussman MA, Gottlieb RA, Glembotski CC. Kinetics of the translocation and phosphorylation of αB-crystallin in mouse heart mitochondria during ex vivo ischemia. Am J Physiol Heart Circ Physiol. 296:H1633-42, 2009. PMC Journal - In Process

  2. Gottlieb RA, Finley KD, Mentzer RM Jr. Cardioprotection requires taking out the trash. Basic Res Cardiol. 104:169-80, 2009. PMC Journal - In Process

  3. Yitzhaki S, Huang C, Liu W, Lee Y, Gustafsson AB, Mentzer RM Jr, Gottlieb RA. Autophagy is required for preconditioning by the adenosine A1 receptor-selective agonist CCPA. Basic Res Cardiol 104:157-67, 2009. PMC Journal - In Process

  4. Perry CN, Kyoi S, Hariharan N, Takagi H, Sadoshima J, Gottlieb RA. Novel methods for measuring cardiac autophagy in vivo. Methods Enzymol.;453:325-42, 2009. PMC Journal - In Process

  5. Gustafsson AB, Gottlieb RA. Autophagy in ischemic heart disease. Circ Res. 104:150-8, 2009. PMC Journal - In Process

  6. Yuan H, Perry CN, Huang C, Iwai-Kanai E, Carreira RS, Glembotski CC, Gottlieb RA. LPS-induced autophagy is mediated by oxidative signaling in cardiomyocytes and is associated with cytoprotection. Am J Physiol Heart Circ Physiol. 296:H470-9, 2009. PubMed Central PMCID: PMC2643899.

  7. Gustafsson AB, Gottlieb RA. Eat your heart out: Role of autophagy in myocardial ischemia/reperfusion. Autophagy 4:416-21, 2008. PMC Journal - In Process

  8. Iwai-Kanai E, Yuan H, Huang C, Sayen MR, Perry-Garza CN, Kim L, Gottlieb RA. A Method to Measure Cardiac Autophagic Flux in vivo. Autophagy 4:322-9, 2008. PMC Journal - In Process

  9. Jin JK, Whittaker R, Glassy MS, Barlow SM, Gottlieb RA, Glembotski CG. Localization of phosphorylated αB-crystallin to heart mitochondria during ischemia-reperfusion. Am J Physiol Heart Circ Physiol. 294:H337-344, 2008. PMC Journal - In Process

  10. Klionsky DJ, Abeliovich H, Agostinis P, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 4:151-175, 2008. PMCID: 18188003

  11. Tsukada YT, Sanna MG, Rosen H, Gottlieb RA. S1P1-Selective Agonist SEW2871 Exacerbates Reperfusion Arrhythmias. J Cardiovasc Pharmacol. 50:660-669, 2007.

  12. Benjamin IJ, Guo Y, Srinivasan S, Boudina S, Taylor R, Rajasekaran NS, Gottlieb RA, Wawrousek E, Abel ED, Bolli R. CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice. Am J Physiol Heart Circ Physiol. 293:H3201-9, 2007.

  13. Brady NR, Hamacher-Brady A, Yuan H, Gottlieb RA. The autophagic response to nutrient deprivation in the HL-1 cardiac myocyte is modulated by Bcl-2 and sarco/endoplasmic reticulum calcium stores. FEBS J. 274:3184-97, 2007.

  14. Hamacher-Brady A, Brady NR, Logue SE, Sayen MR, Jinno M, Kirshenbaum LA, Gottlieb RA, and Gustafsson AB. Response to Myocardial Ischemia/Reperfusion Injury Involves Bnip3 and Autophagy. Cell Death Differ. 14:146-57, 2007.

  15. Hamacher-Brady A, Brady NR, Gottlieb RA. Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac myocytes. J Biol Chem 281:29776-87, 2006.

  16. Hamacher-Brady A, Brady NR, Gottlieb RA, and Gustafsson AB. Autophagy as a protective response to Bnip3-mediated apoptotic signaling in the heart (Addendum). Autophagy 2:307-9, 2006.

  17. Wall JA, Wei J, Ly M, Belmont P, Mardinale JJ, Tran D, Sun J, Chen WJ, Yu W, Oeller P, Briggs S, Gustafsson AB, Sayen MR, Gottlieb RA, and Glembotski CC. Alterations in oxidative phosphorylation complex proteins in the hearts of transgenic mice that overexpress the p38 MAP kinase activator, MAP kinase kinase 6. Am J Physiol Heart Circ Physiol 291:H2462-72, 2006.

  18. Brady NR, Hamacher-Brady A, and Gottlieb RA. Proapoptotic Bcl-2 family members and mitochondrial dysfunction during ischemia/reperfusion injury, a study employing cardiac HL-1 cells and GFP biosensors. Biochim Biophys Acta - Bioenergetics. 1757:667-78, 2006.

  19. Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, and Molkentin JD. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature, 434:658-62, 2005.

  20. Gustafsson AB, Tsai JG, Logue SE, Crow MT, Gottlieb RA. Apoptosis repressor with caspase recruitment domain projects against cell death by interfering with Bax activation. J Biol Chem. 279:21233-21238, 2004.

  21. Granville DJ, Tashakkor B, Takeuchi C, Gustafsson AB, Huang C, Sayen MR, Wentworth P Jr, Yeager M, and Gottlieb RA. Reduction of ischemia and reperfusion-induced myocardial damage by cytochrome P450 inhibitors. Proc Natl Acad Sci U S A 101:1321-6, 2004.

  22. Ricci, JE, Gottlieb, RA, and Green, DR. Caspase-mediated loss of mitochondrial function and generation of reactive oxygen species during apoptosis. J. Cell Biol. 160:65-75, 2003.

  23. Yuan, H, Williams, SD, Adachi, S, Oltersdorf, T, and Gottlieb, RA. Cytochrome c dissociation and release from mitochondria by tBid and ceramide. Mitochondrion. 2:237-244, 2003.

  24. Nijmeijer R, Willemsen M, Meijer CJ, Visser CA, Verheijen RH, Gottlieb RA, Hack CE, Niessen HW. Type II secretory phospholipase A2 binds to ischemic flip-flopped cardiomyocytes and subsequently induces cell death. Am J Physiol Heart Circ Physiol. 285:H2218-24, 2003.

  25. Sayen, MR, Gustafsson, AB, Sussman, MA, Molkentin, JD and Gottllieb, RA. Calcineurin transgenic mice have mitochondrial dysfunction and elevated superoxide production. AJP Cell Physiol 284:C562-70 2003.

  26. Chen, M, Won, D-J, Krajewski, S., and Gottlieb, R.A. Calpain and mitochondria in ischemia/reperfusion injury. J Biol Chem 277:29181-29186, 2002.

  27. Gustafsson, AB, Sayen, MR, Williams, SD, Crow, MT, and Gottlieb, RA. TAT protein transduction into isolated perfused hearts: TAT-ARC is cardioprotective. Circulation 106:735-739, 2002.

  28. Williams, SD, and Gottlieb, RA. Inhibition of mitochondrial calcium-independent phospholipase A2 attenuates mitochondrial pospholipid loss and is cardioprotective. Biochem. J. 362:23-32, 2002.

  29. He, H, Chen, M, Scheffler, NK, Gibson, BW, Spremulli, LL, and Gottlieb, RA. Phosphorylation of mitochondrial elongation factor Tu in ischemic myocardium: Basis for chloramphenicol-mediated cardioprotection. Circ Res 89:461-467, 2001.

  30. Chen, M, He, H, Zhan, S., Krajeewski, S, Reed, JC, and Gottlieb, RA. Bid is cleaved by calpain to an active fragment in vitro and during myocardial ischemia/reperfusion. J Biol Chem 276:30724-30728, 2001.

  31. Yuan, H, Mutomba, MC, Prinz, I, and Gottlieb, RA. Differential processing of cytosolic and mitochondrial caspases. Mitochondrion 1:61-69, 2001.

  32. Gallagher, AM and Gottlieb, RA. Proliferation not apoptosis alters epithelial cell migration in the small intestine of CFTR null mice. Am J Physiol: GI and Liver 281:G681-G696, 2001.

  33. Li, H, Karwatowska-Propkopczuk, E, Mutomba, M, Wu, J, Karanewsky, D, Valentino K, Engler, RL, and Gottlieb, RA. Pharmacology of caspase inhibitors in rabbit cardiomyocytes subjected to metabolic inhibition and recovery. Antioxidants & Redox Signaling, 3:113-123, 2001.

  34. Gottlieb, RA and Adachi, S. Nitrogen cavitation for cell disruption to obtain mitochondria from cultured cells. Meth Enzymol 322:213-221, 2000.

  35. Mutomba, MC, Yuan, H, Konyavko, M, Adachi, S, Yokoyama, CB, Esser, V, McGarry, JD, Babior, BM, and Gottlieb, RA. Regulation of the activity of caspases by L-carnitine & palmitoylcarnitine. FEBS Lett., 478:12-25, 2000.

  36. He, H, Li, H, Lin, A, and Gottlieb, RA. Activation of the JNK pathway is important for cardiomyocyte death in response to simulated ischemia. Cell Death and Differentiation, 6:987-991, 1999.

  37. Suzuki, H, Delano, FA, Jamshidi, N, Katz, D, Mori, M, Kosaki, K, Gottlieb, RA, Ishii, H, and Schmid-Schoenbein, GW. Enhanced DNA fragmentation in the thymus of spontaneously hypertensive rats. Am J Physiol 276 (Heart Circ. Physiol. 45): H2135-2140, 1999.

  38. Adachi, S, Gottlieb, RA, and Babior, BM. Lack of release of cytochrome c from mitochondria into cytosol early in the course of Fas-mediated apoptosis of Jurkat cells. J.Biol.Chem. 273:19892-19894, 1998.

  39. Karwatowska-Prokopczuk, E, Nordberg, JA, Li, HL, Engler, RL, and Gottlieb, RA. Effect of vacuolar proton ATPase on intracellular pH, calcium, and on apoptosis in neonatal cardiomyocytes during metabolic inhibition/recovery. Circ Res 82:1139-1144, 1998.

  40. Niessen, H, Meisenholder, G.W., Li, H-L, Gluck, SL, Lee, BS, Forgac, M. Bowman, B, Engler, RL, Babior, BM, Gottlieb, RA. G-CSF upregulates the vacuolar proton ATPase in human neutrophils. BLOOD 90:4598-4601, 1997.

  41. Adachi, S, Cross, AR, Babior, BM, and Gottlieb, RA. Bcl-2 and the outer mitochondrial membrane in the inactivation of cytochrome c during Fas-mediated apoptosis. J.Biol.Chem. 272:21878-21882, 1997.

  42. Krippner, A, Yagi, A, Gottlieb, RA, and Babior, BM. Loss of function in cytochrome c in Jurkat cells undergoing Fas-mediated apoptosis. J Biol Chem 271:21629-21636, 1996.

  43. Meisenholder, GW, Martin, SJ, Green, DR, Nordberg, J, Babior, BM, and Gottlieb, RA. Events in apoptosis: Acidification is downstream of protease activation and Bcl-2 protection. J Biol Chem 271:16260-16262, 1996.

  44. Gottlieb, RA, Zhu, JY, Gruol, D, and Engler, RL. Preconditioning in rabbit cardiomyocytes: Role of pH, vacuolar proton ATPase, and apoptosis. J Clin Invest 97:1-8, 1996.

  45. Gottlieb, RA, Nordberg, J, Skowronski, E, & Babior, BM. Apoptosis induced in Jurkat cells by several agents is preceded by intracellular acidification. Proc Natl Acad Sci USA. 93:654-658, 1996.

  46. Gottlieb, RA, Giesing, HA, Engler, RL, & Babior, BM. The acid deoxyribonuclease of neutrophils: A possible participant in apoptosis-associated genome destruction. BLOOD 86:2414-2418, 1995.

  47. Gottlieb, RA, Giesing, HA, Zhu, JY, Engler, RL, & Babior, BM. G-CSF prevents apoptosis in neutrophils by activating the vacuolar H+-ATPase. Proc Natl Acad Sci USA. 92:5965-8, 1995.

  48. Gottlieb, RA, Burleson, KO, Kloner R, Babior, BM, & Engler, RL. Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 94:1621-28, 1994.

Research Support


Ongoing

1 R01 AG021568-06 • (Gottlieb) • 08/01/03-07/31/09 (no cost-extension) • NIH/NIA
Bid-mediated Cytochrome c Release from Mitochondria
The major goal(s) of this project: 1) assess effect of BH3 proteins on cardiolipin; 2) assess effect of BH3 proteins on interaction between cytochrome c and electron transfer complexes; and 3) assess effect of Bcl-2 and Bcl-xL on BH3-mediated events.

1 P01 HL085577-01 • (Sussman) • 07/01/06-06/30/11 • NIH/NHLBI
Protecting Myocardium by Enhancing Mitochondrial Integrity
The major goals of this project: 1) Establish whether autophagy is protective or deleterious in I/R; 2) identify triggers of autophagy; 3) delineate roles of Akt/AMPK, mTOR; 4) evaluate autophagy in post-infarct remodeling and hypertrophy.

5 R01AG033283 • (Gottlieb) • 03/15/08 - 02/28/13 • NIH/NIA
Subcellular Regulation of Autophagic Flux in Cardiomyocytes and the Heart
The major goals of this project: 1) Develop methods to measure organelle-selective autophagic flux; 2) Examine the role of Bcl-2 family members in regulating autophagy; 3) Assess mitochondrial fission and fusion in relation to autophagy; 4) evaluate autophagy in vivo in the context of the cardiac response to bacterial endotoxin.

5R01HL060590-12 • (Gottlieb) • 09/01/98 - 05/31/12 • NIH/NHLBI
Rescue and Role of Complex I in Myocardial Ischemic Injury
The goal of this project is to assess the roles of Bid, Bax, and p38MAPK in the mitochondrial permeability transition pore (MPTP); to assess the potential role of Complex I in the MPTP; to determine whether (and how) cyclophilin D regulates Complex I; and to assess the cardioprotective potential of recombinant tat-Ndi1.

1R01HL092136-01A1 • (Gottlieb/Gustafsson) • 12/19/08 - 11/30/13 • NIH/NHLBI
Juvenile Mouse Model of Delayed Anthracycline Cardiotoxicity
The major goals of this project are to 1) Characterize functional, structural, and cellular alterations in a mouse model of pediatric anthracycline exposure late onset cardiotoxicity, 2) Evaluate the effects of doxorubicin on the cardiac stem cell (CSC) population, 3) Elucidate effects of doxorubicin on bone marrow-derived stem cells (BMSC) in cardiac repair, and 4) Investigate therapeutic potential of stem cell engraftment to prevent late-onset cardiotoxicity.

Completed

1 R01 HL71091-01A2 • (Gottlieb) 12/01/03-11/30/08 • (no-cost extension) • NIH/NHLBI
Cytochrome P450 in Reperfusion Injury
The major goals of this project: 1) Characterize efficacy of sulfaphenazole in cardioprotection; 2) Characterize the mechanism of cardioprotection by sulfaphenazole; 3) Survey the roles of CYP in cardiac dysfunction and apoptosis.