People

Lear BraceLear photo

Ph.D. Candidate

Education:

B.S. Emmanuel College

Research Interests:

My main research focus is studying the effects of DNA damage on energy metabolism. Utilizing a mouse model of Cockayne syndrome (a progeroid disorder caused by defects in DNA repair and characterized by progressive lipodystrophy and reduced lifespan, among many other phenotypes) as a tool, I am exploring how genotoxic stress mediates alterations in fat and energy metabolism.

Select publications:

Hine, E. Harputlugil, Y. Zhang, C. Ruckenstuhl, B.C. Lee, L. Brace, A. Longchamp, J.H. Trevin ̃o-Villarreal, P. Mejia, C. K. Ozaki, R. Wang, V.N. Gladyshev, F. Madeo, W.B. Mair, and J.R. Mitchell. Endogenous Hydrogen Sulfide Production Is Essential for Dietary Restriction Benefits, Cell (2015), http://dx.doi.org/10.1016/j.cell.2014.11.048

Fang EF, Scheibye-Knudsen M, Brace LE, Kassahun H, SenGupta T, Nilsen H, Mitchell JR, Croteau DL, Bohr VA. Defective mitophagy in XPA via PARP-1 hyperactivation and NAD(+)/SIRT1 reduction. Cell. 2014 May 8;157(4):882-96.

Brace LE, Vose SC, Vargas DF, Zhao S, Wang XP, Mitchell JR. Lifespan extension by dietary intervention in a mouse model of Cockayne syndrome uncouples early postnatal development from segmental progeria. Aging Cell. 2013 Dec;12(6):1144-7.
 

Eylul HarputlugilEylul photo

Ph.D. candidate, Biological Science in Public Health Program, Harvard University

Education:

B.Sc., Biological Science and Bioengineering, Sabanci University, Turkey

M.Sc., Molecular Biology and Genetics, Bilkent University, Turkey

Research Interests:

My research interests include understanding the roles of amino acid sensing pathways mTORC1 and GCN2 in sensing dietary protein restriction and mediating its beneficial effects such as protection from surgical stress. Additionally, I am working on the regulation of hydrogen sulfide producing enzymes CGL and CBS by upstream nutrient and hormone sensing pathways.

Select Publications:

Harputlugil E, Hine C, Vargas D, Robertson L, Manning BD, Mitchell JR. “The TSC complex is required for the benefits of dietary protein restriction on stress resistance in vivo.” Cell Rep. 2014 Aug 21;8(4):1160-70.

Gallinetti J, Harputlugil E, Mitchell JR.”Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR.” Biochem J. 2013 Jan 1;449(1):1-10.

Menon S, Yecies JL, Zhang HH, Howell JJ, Nicholatos J, Harputlugil E, Bronson RT, Kwiatkowski DJ, Manning BD. “Chronic activation of mTOR complex 1 is sufficient to cause hepatocellular carcinoma in mice.” Sci Signal. 2012 Mar 27;5(217):ra24

 

Christopher HineChris photo

Postdoctoral Research Fellow 

Education:

Youngstown State University (BS)

University of Rochester (MS, PhD)

Research Interests:

My research interests are in cellular and organismal adaptive responses stimulated by dietary restriction. These adaptive responses stem from low levels of stress originating from metabolic changes due to reduced caloric intake and/or alterations in amino acid composition and elicit stress resistance and prevent aging-related pathologies. Specifically, I investigate the nutritional and genetic requirements for increasing endogenous hydrogen sulfide (H2S) production in various organs and tissues as well as the requirement of this increased H2S for the benefits of dietary restriction. Doing so allows for improved dietary and/or pharmacological interventions to elicit beneficial endogenous H2S exposure for improved healthspan, lifespan and clinical outcomes.

Select Publications: 

Hine, C.; Mitchell, J. Calorie Restriction and Methionine Restriction in Control of Endogenous Hydrogen Sulfide Production by the Transsulfuration Pathway. Experimental Gerontology (in press)

Hine, C.; Harputlugil, E.; Zhang, Y.; Ruckenstuhl, C.; Lee, B.C.; Brace, L.E.; Longchamp, A.; Trevino-Villarreal, J.H.; Mejia, P.; Ozaki, C.K.; Wang, R.; Gladyshev, V.N.; Madeo, F.; Mair, W.B.; Mitchell, J.R. Endogenous Hydrogen Sulfide Production is Essential for Dietary Restriction Benefits. Cell (2014).

Harputlugil, E; Hine, C; Vargas, D; Robertson, L; Manning, B; Mitchell, J. The TSC Complex Is Required for the Benefits of Dietary Protein Restriction on Stress Resistance in vivo. Cell Reports (2014).

Hine, C.; Mitchell, J. Saying No to Drugs: Fasting Protects Hematopoietic Stem Cells from Chemotherapy and Aging. Cell Stem Cell (2014).

Hine, C.; Li, H.; Xie, L.; Mao, Z.; Seluanov, A.; Gorbunova, V. Regulation of Rad51 Promoter. Cell Cycle (2014).

Tian, X*; Azpurua, J*; Hine, C*; Vaidya, A; Myakishev-Rempel, M; Ablaeva, J; Mao, Z; Nevo, E; Gorbunova, V; Seluanov, A. High-molecular-mass Hyaluronan Mediates the Cancer Resistance of the Naked Mole Rat. Nature (2013). *These authors contributed equally.

Gorbunova, V.; Hine, C.; Tian, X.; Ablaeva, J.; Gudkov, A.V.; Nevo, E.; Seluanov, A. Cancer Resistance in the Blind Mole Rat is Mediated by Concerted Necrotic Cell Death Mechanism. PNAS (2012).

Hine, C.; Mitchell, J. NRF2 and the Phase II Response in Acute Stress Resistance Induced by Dietary Restriction. Published in the special issue “Mechanisms of Aging and Longevity”, edited by David Lombard. Journal of Clinical and Experimental Pathology (2012).

Fong, V; Osterbur, M; Capella, C; Kim, Y; Hine, C; Seluanov, A; Gorbunova, V; Dewhurst, S. Adenoviral Vector Driven by a Minimal Rad51 Promoter is Selective for p53-Deficient Tumor Cells. PLoS One (2011).

Hine, C; Seluanov, A; Gorbunova, V. Rad51 Promoter Targeted Gene Therapy is Effective for in vivo Visualization and Treatment of Cancer. Molecular Therapy (2011).

Mao, Z; Hine, C; Tian, X; Van Meter, M; Au, M; Vaidya, A Vaidya; Seluanov, A; Gorbunova, V. SIRT6 Promotes DNA Repair Under Stress by Activating PARP1. Science (2011).

Seluanov, A; Hine, C; Azpurua, J; Feigenson, M; Bozzella, M; Mao, Z; Catania, K Gorbunova, V. Hypersensitivity to Contact Inhibition Provides a Clue to Cancer Resistance of Naked Mole-Rat. PNAS (2009).

Hine, C; Seluanov, A; Gorbunova, V. Use of the Rad51 Promoter for Targeted Anti-Cancer Therapy. PNAS (2008).

Seluanov, A; Hine, C; Bozzella, M; Hall, A; Sasahara, T; Ribeiro, A; Catania, K; Presgraves, D; Gorbunova, V. Distinct Tumor Suppressor Mechanisms Evolve in Rodent Species that Differ in Size and Lifespan. Aging Cell (2008).

Gorbunova, V; Seluanov, A; Mao, Z; Hine, C. Changes in DNA Repair During Aging. Nucleic Acids Research (2007).

Seluanov, A; Chen, Z; Hine, C; Sasahara, T; Ribeiro, A Catania, K; Presgraves, D; Gorbunova, V. Telomerase Activity Coevolves with Body Mass, Not Lifespan. Aging Cell (2007).

 

Alban LongchampAlban photo

Graduate student

Education:

Bachelor in Medicine, University of Lausanne, Switzerland

Master in Medicine, University of Lausanne, Switzerland

Research interests:

My major research interests lie in vascular biology and adaptation to low level of nutrients. I am interested in how amino acids sensing pathways regulate vessels growth, function under physiological conditions and pathological remodeling upon trauma such as vascular surgery.

Selected publications:

Hine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, Longchamp A, Treviño-Villarreal JH, Mejia P, Ozaki CK, Wang R, Gladyshev VN, Madeo F, Mair WB, Mitchell JR. Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell 2014 (in press)

Longchamp A, Allagnat F, Berard X, Alonso F, Haefliger JA, Deglise S, Corpataux JM. Procedure for human saphenous veins ex vivo perfusion and external reinforcement. J Vis Exp. 2014 Oct 1

Mauro CR, Ding K, Xue H, Tao M, Longchamp A, Belkin M, Kristal BS, Ozaki CK. Adipose phenotype predicts early human autogenous arteriovenous hemodialysis remodeling. J Vasc Surg. 2014 Sep 26.

Mauro CR, Tao M, Yu P, Treviño-Villerreal JH, Longchamp A, Kristal BS, Ozaki CK, Mitchell JR. Preoperative dietary restriction reduces intimal hyperplasia and protects from ischemia-reperfusion injury. J Vasc Surg. 2014 Aug 8

Longchamp A, Alonso F, Dubuis C, Allagnat F, Berard X, Meda P, Saucy F, Corpataux JM, Déglise S, Haefliger JA. The use of external mesh reinforcement to reduce intimal hyperplasia and preserve the structure of human saphenous veins. Biomaterials. 2014 Mar;35

 

Pedro MejiaPedro photo

Yerby Postdoctoral Research Fellow

Education:

Ph.D. Immunology (Pasteur Institute, Paris, France)

Research Interests:

I am interested in elucidating immuno-pathogenic mechanisms of cerebral malaria in order to identify potential pharmacological targets that can modulate the severity of the disease.

Select Publications:

Mejia P, Treviño-Villarreal JH, Hine C, Harputlugil E, Lang S, Calay E, Rogers R, Wirth D, Duraisingh MT, Mitchell JR. Modulation of leptin by short-term dietary restriction protects from experimental cerebral malaria via mTORC1 suppression. Nature communications (in press, 2014)

Peng W, Robertson L, Gallinetti J, Mejia P, Vose S, Charlip A, Chu T, Mitchell JR, Surgical Stress Resistance Induced by Single Amino Acid Deprivation Requires Gcn2 in Mice. Sci Transl Med. 25 January 2012: Vol. 4, Issue 118, p. 118.

Arnold l, Tyagi RK, Mejia P, Swetman C, Gleeson J,  Pérignon JL, Druilhe P. Further improvements of the P. falciparum humanized mouse model.  PloS one. 01/2011; 6(3):e18045.

Druilhe P, Spertini F, Soesoe D, Corradin G, Mejia P, Singh S, Audran R, Bouzidi A, Oeuvray C, Roussilhon C.  A malaria vaccine that elicits in humans antibodies able to kill Plasmodium falciparum. PLoS Med. 2005 Nov; 2(11):e344.

Singh S, Soe S, Mejia P, Roussilhon C, Theisen M, Corradin G, Druilhe P.   Identification of a conserved region of Plasmodium falciparum MSP3 targeted by biologically active antibodies to improve vaccine design. J INFECT DIS. 2004 SEP 1; 190(5):1010-8.

 

Humberto TreviñoHumberto

Research Associate

Education:

Ph.D in Immunology (2009) Universidad Autónoma de Nuevo León, Monterrey, Mexico

M.D. (2006) Universidad Autónoma de Nuevo León Medical School

Research interests:

I am interested in the effects of nutrition on metabolism.

Selected publications:

Mejia P, Treviño-Villarreal JH, Hine C, Lang S, Calay E, Rogers R, Wirth D, Duraisingh M, Mitchell JR. Modulation of host adipokine leptin by short-term dietary restriction protects from experimental cerebral malaria via suppression of mTORC1. Nat Comm 2014 (in press)

Hine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, Longchamp A, Treviño-Villarreal JH, Mejia P, Ozaki CK, Wang R, Gladyshev VN, Madeo F, Mair WB, Mitchell JR. Endogenous hydrogen sulfide production is essential for dietary restriction benefits. Cell 2014 (in press)

Mauro CR, Tao M, Peng Y, Treviño-Villerreal JH, Longchamp A, Kristal BS, Ozaki CK, Mitchell JR. Pre-operative dietary restriction reduces intimal hyperplasia and protects from ischemia reperfusion injury. J Vasc Surg 2014 Aug 8. pii: S0741-5214(14)01295-6. PMID: 25124359