Resume

• 2008

  Doctor of Medicine (MD)

  Stanford University School of Medicine

  Doctor of Philosophy (PhD)

  Thesis advisors: K. Christopher Garcia and Irving Weissman

  Structural Biology

  Stanford University School of Medicine

• 2004

  Bachelor of Science (BS)

  Awarded the Paul Sigler memorial prize as the top undergraduate student in the Molecular Biophysics and Biochemistry Department.

  Molecular Biophysics and Biochemistry

  Yale University

  Magna cum laude

  Master of Science (MS)

  Thesis advisor: Richard Lifton

  Molecular Biophysics and Biochemistry

  Yale University

• Molecular Biology

  Protein Engineering

  Cancer

  Drug Discovery

  Immunology

  Biophysics

  X-ray crystallography

  Structural Biology

  Biochemistry

  Directed Evolution

  Engineered SIRPα variants as immunotherapeutic adjuvants to anticancer antibodies

  Cancer cells avoid immune destruction by macrophages using a protein called CD47

  which acts as a molecular \"don't eat me signal.\" Using directed evolution

  we engineered a variant of CD47's receptor

  SIRPα

  to antagonize CD47 with extremely high affinity. The high-affinity SIRPα molecules show efficacy as monotherapy for mouse models of human cancer when fused to antibody-Fc. However

  as small (14 kDa) monomers

  the variants act as powerful adjuvants to anti-cancer antibodies

  including Rituxan and Herceptin. As antibodies are a rapidly growing class of therapeutics

  the high-affinity SIRPα proteins have great therapeutic potential for a wide variety of clinical scenarios.

  Engineered SIRPα variants as immunotherapeutic adjuvants to anticancer antibodies

  Adrenaline-activated structure of β2-adrenoceptor stabilized by an engineered nanobody

  Mechanistic and structural insight into the functional dichotomy between IL-2 and IL-15

  Activation and allosteric modulation of a muscarinic acetylcholine receptor

  Interleukin-2 (IL-2) is a pro-inflammatory cytokine that is used clinically in the treatment of metastatic melanoma and renal cell carcinoma. Though it can induce a long-lasting remission in a small fraction of patients

  IL-2 is limited by life-threatening side-effects such as pulmonary edema. In this study

  we engineered IL-2 to have enhanced anti-tumor efficacy

  while decreasing its toxic side effects

  thereby increasing its therapeutic window and potentially extending its clinical effectiveness.

  Exploiting a natural conformational switch to engineer an interleukin-2 'superkine'

  Ring

  Simcha Therapeutics

  Yale School of Medicine

  Stanford University School of Medicine

  Yale University

  New Haven

  Connecticut

  Founder

  Simcha Therapeutics

  I completed my PhD in Structural Biology in the laboratories of K. Christopher Garcia and Irving Weissman concurrently with my medical training. My research focused on using directed evolution to engineer new immunomodulatory agents for the treatment of cancer and autoimmune disease. Additionally

  I developed new methodologies with Brian Kobilka's laboratory to extend combinatorial techniques to integral membrane proteins such as G-protein coupled receptors.

  Stanford University School of Medicine

  Yale School of Medicine

  Assistant Professor of Immunobiology

  Yale School of Medicine

  During my undergraduate training

  I performed research on the molecular genetics of hypertension in the laboratory of Richard Lifton.

  Beckman Scholar

  Yale University

  PCT/US2011/066911

  High Affinity Sirp-Alpha Reagents

  NIH Director's Early Independence Award (DP-5) Recipient

  National Institutes of Health

  Phi Beta Kappa

  Yale University

  Forbes 30 under 30 in Healthcare

  Forbes Magazine

  Pew-Stewart Scholar

  The Pew Charitable Trusts

  Barry M. Goldwater Scholar

  Barry M. Goldwater Foundation

  Ruth L. Kirschstein National Research Service Award

  National Institutes of Health

  Beckman Scholar

  Arnold and Mabel Beckman Foundation

  Robert T. McCluskey Yale Scholar

  Yale School of Medicine

  Paul Sigler Memorial Award

  Yale Dept. of Molecular Biophysics and Biochemistry