C. Keith Ozaki, M.D.

Professor
Department of Surgery
Brigham and Women's Hospital/Harvard Medical School
Boston, MA

Primary Research:

Our basic research efforts broadly aim to delineate the mechanisms by which physical forces alter the morphology of the blood vessel wall.  We hold expertise specifically in the adaptations of the vein bypass graft, an extreme example of acute perturbation of the hemodynamic environment combined with vascular trauma.  The strength of our approach is a network of key collaborators at Harvard (e.g. Dr. James R. Mitchell) and beyond who synergistically partner with us to better the lives of patients with vascular disease.

Recent investigative efforts have focused on inflammatory, adipose, and hydrogen sulfide driven mechanisms of vascular adaptations to physical forces.  Emerging directions expand (in both animal models and humans) this foundation of knowledge into links between short-term dietary restriction and subsequent endogenous hydrogen sulfide upregulation, adipose biology, and robust analyses of the longitudinal interplay between local hemodynamic factors and such biologic mediators.

Finally, as a clinician-scientist led group we also hold a diverse but complementary clinical research portfolio, and we leverage our clinical research enterprise to accelerate translational steps for our basic research.

Lab Web Site: http://bvsrl.bwh.harvard.edu/Ozaki_Lab.html

Members of the laboratory:

C. Keith Ozaki, M.D.—Principle Investigator
Ming Tao, M.D.—Laboratory Director and Research Specialist
Kaspar Trocha, M.D.— Post-doctoral fellow
Peter Kip, M.D.— Post-doctoral fellow
Jennifer M. Giulietti—Clinical Research Associate
James J. O’Leary—Clinical Research Associate
Jack Ruske—Clinical Research Associate
Lorraine Levitsky, Director, Vascular Surgery

Recent Publications:

• Hine C, Harputlugil E, Zhang Y, Ruckenstuhl C, Lee BC, Brace L, Longchamp A, Trevino-Villarreal JH, Mejia P, Ozaki CK, Wang R, Gladyshev VN, Madeo F, Mair W, Mitchell JR.  Endogenous hydrogen sulfide production is essential for dietary restriction benefits.  Cell 2015; 160(1-2):132-144.
• Sharma G, Tao M, Ding M, Yu D, King W, Deyneko G, Wang X, Longchamp A, Schoen FJ, Ozaki CK, Semel ME.  Perivascular adipose adiponectin correlates with symptoms status of patients undergoing carotid endarterectomy. Stroke 2015;46:1696-1699.
• Longchamp A, Tao M, Bartlelt A, Ding K, Lynch L, Hine C, Corpataux J, Kristal BS, Mitchell JR, Ozaki CK.  Surgical injury induces local and distant adipose tissue browning.  Adipocyte 2015;20(2):163-174.
• Mauro C, Ding K, Xue H, Tao M, Longchamp A, Belkin M, Kristal B, Ozaki CK.  Adipose phenotype predicts human arteriovenous fistula remodeling.  J Vasc Surg 2016;63:171-176.
• Mauro CR, Tao M, Yu P, Trevino-Villerreal JH, Longchamp A, Kristal BS, Ozaki CK, Mitchell JR.  Pre-operative dietary restriction reduces intimal hyperplasia and protects from ischemia reperfusion.  J Vasc Surg 2016;63(2):500-509.
• Hine C, Kim HJ, Zhu Y, Harputlugil E, Longchamp A, Matos MS, Ramadoss P, Bauerle K, Brace L, Asara JM, Ozaki CK, Cheng SY, Singha S, Ahn KH, Kimmelman A, Fisher Fm, Pissios P, Withers DJ, Selman C, Wang R, Yen K, Longo VD, Cohen P, Bartke A, Kopchick JJ, Miller R, Hollenbery AN, Mitchell JR.  Hypothalamic-Pituitary axis regulates hydrogen sulfide production.  Cell Metab 2017; 25(6):1320-1333.
• Mirabella T, MacArthur JW, Cheng D, Ozaki CK, Yoo YJ, Yang M, Chen CS.  3D printed vascular networks direct therapeutic angiogenesis in ischemia.  Nat Biomed Eng 2017; 10.1038/s41551-017-0083.
• Sharma G, Kuppler C, Yong H, Tao M, Ding K, Longchamp A, Dember L, Ozaki CK, Berceli SA.  Local adipose-associated mediators and adaptations following arteriovenous fistula creation.  Kidney Int Reports 2018; https://doi.org/10.1016/j.ekir.2018.02.008.
• Longchamp A, Mirabella T, Adruini A, MacArthur M, Das Abhirup, Treviño-Villarreal JH, Hine C, Ben-Sahra I, Knudsen N, Brace LE, Reynolds J, Mejia P, Tao M, Sharma G, Wang R, Corpataux JM, Haefliger JA, Ahn KH, Lee CH, Manning BD, Sinclair DA, Chen C, Ozaki CK, Mitchell JR.  Amino acid restriction triggers angiogenesis via GCN2/ATF4 regulation of VEGF and H2S production.  Cell 2018;173(1):117-129.
• Greco Song H.-H, Cumma, RT, Ozaki CK, Edelman ER, Chen CS.  Vascular tissue engineering: progress, challenges, and clinical promise.  Cell Stem Cell 2018; 22(3):340-354.

Collaborative Relationships:

• Masanori Aikawa, Ph.D.—https://aikawalabs.bwh.harvard.edu/
• Scott A. Berceli, M.D., Ph.D.—https://surgery.med.ufl.edu/research/vascular-biology/scott-a-berceli-m-d-ph-d/
• Christopher S. Chen, M.D., Ph.D.—https://sites.bu.edu/chenlab/
• Karen J. Ho, M.D.—http://www.feinberg.northwestern.edu/faculty-profiles/az/profile.html?xid=28371
• James R. Mitchell, Ph.D.—https://www.hsph.harvard.edu/james-mitchell/
• Paul H. A. Quax, Ph.D. and Margreet R. De Vries, Ph.D.—http://www.einthovenlaboratory.com/

Laboratory Motto:

“Nothing but the Truth!”