Past Members

Lear Brace
Lear photoTitle:
PhD Candidate

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.


Christopher Hine
Chris photoTitle:
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 Longchamp
Alban photo

Title:
Research 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


Sarah Vose
Sarah Vose (vose_mitchelllab.jpg) 

Postdoctoral Research Fellow

Education:  Ph.D., University of California, Berkeley; B.S., Vanderbilt University

Research Interests:

In the Mitchell laboratory, I study Cockayne Syndrome (CS), a premature aging disease caused by a defect in transcription-coupled nucleotide excision repair (TC-NER). TC-NER removes helix-distorting lesions from the transcribed strand of DNA.  Symptoms of CS include loss of fat, neuron degeneration and dwarfism; the average lifespan is 12.5 years.  There is no cure for CS, and it us unclear how unrepaired DNA damage can lead to such drastic whole-body changes.  We are currently exploring mechanisms underlying CS including sensitivity to oxidative stress and alternate energy metabolism.  We hope to identify the primary target tissue of CS and uncover important molecular points of intervention for the disease.

Publications:

Vose, SC, Fujioka, K, Gulevich, AG, Lin, AY, Holland, NT, Casida, JE.  Cellular function of neuropathy target esterase in lysophosphatidylcholine action.  Toxicol Appl Pharm (2008), 232, 376- 383.

Casida JE, Nomura DK, Vose SC.  Organophosphate-sensitive lipases modulate brain lysophospholipids, ether lipids and endocannabinoids.  Chem Biol Interact (2008), 175, 355- 364. 

Vose SC, Holland NT, Eskenazi B, Casida JE.  Lysophosphatidylcholine hydrolases of human erythrocytes, lymphocytes and brain: sensitive targets of conserved specificity for organophosphorus delayed neurotoxicantsToxicol Appl Pharm (2007), 224, 98- 104.

Quistad BG, Fisher KJ, Owen SC, Klintenberg R, Casida JE.  Platelet-activating factor acetylhydrolase: selective inhibition by potent n-alkyl methylphosphonofluoridates.  Toxicol Appl Pharm (2005) 205, 149-156.


Lauren Robertson

Lauren Robertson (robertson_mitchelllab.jpg)

Research Assistant

Education:  Smith College, 2009

Research Interests:

I use models of surgical ischemia reperfusion injury to study short-term dietary preconditioning regimens conveying maximal stress resistance, as measured by organ function and survival. I am also interested in the essential nutritional components responsible for conveying this protection, and choose to interrogate this question through various dietary, molecular, and genetic manipulations.  My research focuses on identifying biomarker(s) of stress resistance, an effector organ, and a genetic model in order to elucidate mechanisms of adaptive stress resistance.   During my free time, I enjoy travel, sports, live music, and time outside.

Publications:

Peng WRobertson LGallinetti 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.


Jordan Gallinetti

Jordan Gallinetti (jordan_mitchelllab.jpg)

Graduate Student

Education: B.S., Biology; Minor, Nutrition; Drexel University, 2010

Research Interests:

My research focuses on modulation of dietary amino acids to confer stress resistance to acute oxidative insults in mice. I am also interested in the systemic changes in lipid metabolism and handling, and the essential genetic components that may contribute to this stress resistance. In my free time, I enjoy cooking, watching sports, traveling, and writing about food.

Publications:

Peng WRobertson L, Gallinetti JMejia 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.

Technical Reviewer: Takemura,Masaharu, Kikuyaro, and Office Sawa. TheManga Guide to Biochemistry. San Francisco: No Starch Press, 2011.


Eylul Harputlugil

 

 

 

 

 

 

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

 


Allison Charlip

Allison Charlip (allison_charlip.jpg)

Research Assistant

Education: University of Virginia, 2009

Research Interests:

Allison primarily focuses on the effects of ischemic reperfusion injury, particularly on the histological level. Using renal and hepatic histological samples, Allison examines the varying levels of acute injury due to oxidative stress and resulting tissue damage.

Allison is simultaneously pursuing a career in veterinary medicine. She enjoys skiing in the winter and sailing during the summer. She also likes to take advantage of everything Boston has to offer- from new restaurants to Red Sox games.


Wei Peng

Wei Peng (wei_peng.jpg) 

Postdoctoral Research Fellow

Education:  Ph.D., Harvard University

Research Interests:

Wei is interested in the effect of nutritional preconditioning on acute stress resistance. She is currently using a mouse model of ischemia reperfusion injury to study the pathways triggered by amino acid deficiency. Some of the questions she is exploring are: 1) the role of GCN2 kinase, an amino acid sensor, in stress resistance; 2) the impact of short-term nutrient deprivation on the innate immune system.

Outside of work she is a food connoisseur who vows to dig up all the hidden gems in Boston.

Select Publications:

Vincent MS, Xiong X, Grant EP, Peng W, Brenner MB. CD1a-, b-, and c-restricted TCRs recognize both self and foreign antigens. J Immunol. 2005 Nov 15;175(10):6344-5.

Ellison KS, Peng W, McFadden G. Mutations in active-site residues of the uracil-DNA glycosylase encoded by vaccinia virus are incompatible with virus viability. J Virol. 1996 Nov;70(11):7965-73.