Bio

Professional Education


  • Doctor of Philosophy, University of California Berkeley (2010)
  • Bachelor of Science, Stanford University, BIOL-BSH (2003)
  • Bachelor of Science, Stanford University, MATH-BS (2003)

Stanford Advisors


Publications

Journal Articles


  • Engineered SIRP alpha Variants as Immunotherapeutic Adjuvants to Anticancer Antibodies SCIENCE Weiskopf, K., Ring, A. M., Ho, C. C., Volkmer, J., Levin, A. M., Volkmer, A. K., Oezkan, E., Fernhoff, N. B., van de Rijn, M., Weissman, I. L., Garcia, K. C. 2013; 341 (6141): 88-91
  • Engineered SIRPa variants as immunotherapeutic adjuvants to anticancer antibodies. Science Weiskopf, K., Ring, A. M., Ho, C. C., Volkmer, J., Levin, A. M., Volkmer, A. K., Ozkan, E., Fernhoff, N. B., van de Rijn, M., Weissman, I. L., Garcia, K. C. 2013; 341 (6141): 88-91

    Abstract

    CD47 is an antiphagocytic signal that cancer cells employ to inhibit macrophage-mediated destruction. Here, we modified the binding domain of human SIRPα, the receptor for CD47, for use as a CD47 antagonist. We engineered high-affinity SIRPα variants with approximately 50,000-fold increased affinity for human CD47 relative to wild-type SIRPα. As high-affinity SIRPα monomers, they potently antagonized CD47 on cancer cells but did not induce macrophage phagocytosis on their own. Instead, they exhibited remarkable synergy with all tumor-specific monoclonal antibodies tested by increasing phagocytosis in vitro and enhancing antitumor responses in vivo. This "one-two punch" directs immune responses against tumor cells while lowering the threshold for macrophage activation, thereby providing a universal method for augmenting the efficacy of therapeutic anticancer antibodies.

    View details for DOI 10.1126/science.1238856

    View details for PubMedID 23722425

  • Anti-CD47 antibody-mediated phagocytosis of cancer by macrophages primes an effective antitumor T-cell response PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Tseng, D., Volkmer, J., Willingham, S. B., Contreras-Trujillo, H., Fathman, J. W., Fernhoff, N. B., Seita, J., Inlay, M. A., Weiskopf, K., Miyanishi, M., Weissman, I. L. 2013; 110 (27): 11103-11108

    Abstract

    Mobilization of the T-cell response against cancer has the potential to achieve long-lasting cures. However, it is not known how to harness antigen-presenting cells optimally to achieve an effective antitumor T-cell response. In this study, we show that anti-CD47 antibody-mediated phagocytosis of cancer by macrophages can initiate an antitumor T-cell immune response. Using the ovalbumin model antigen system, anti-CD47 antibody-mediated phagocytosis of cancer cells by macrophages resulted in increased priming of OT-I T cells [cluster of differentiation 8-positive (CD8(+))] but decreased priming of OT-II T cells (CD4(+)). The CD4(+) T-cell response was characterized by a reduction in forkhead box P3-positive (Foxp3(+)) regulatory T cells. Macrophages following anti-CD47-mediated phagocytosis primed CD8(+) T cells to exhibit cytotoxic function in vivo. This response protected animals from tumor challenge. We conclude that anti-CD47 antibody treatment not only enables macrophage phagocytosis of cancer but also can initiate an antitumor cytotoxic T-cell immune response.

    View details for DOI 10.1073/pnas.1305569110

    View details for Web of Science ID 000321978000057

    View details for PubMedID 23690610

  • Synthesis of a photocaged tamoxifen for light-dependent activation of Cre-ER recombinase-driven gene modification. Chemical communications Inlay, M. A., Choe, V., Bharathi, S., Fernhoff, N. B., Baker, J. R., Weissman, I. L., Choi, S. K. 2013; 49 (43): 4971-4973

    Abstract

    We report the design of a water-soluble, quaternized tamoxifen photoprobe and demonstrate its application in light-controlled induction of green fluorescent protein expression via a Cre-ER recombinase system.

    View details for DOI 10.1039/c3cc42179a

    View details for PubMedID 23612712

  • Heme-assisted S-Nitrosation Desensitizes Ferric Soluble Guanylate Cyclase to Nitric Oxide JOURNAL OF BIOLOGICAL CHEMISTRY Fernhoff, N. B., Derbyshire, E. R., Underbakke, E. S., Marletta, M. A. 2012; 287 (51): 43053-43062

    Abstract

    Nitric oxide (NO) signaling regulates key processes in cardiovascular physiology, specifically vasodilation, platelet aggregation, and leukocyte rolling. Soluble guanylate cyclase (sGC), the mammalian NO sensor, transduces an NO signal into the classical second messenger cyclic GMP (cGMP). NO binds to the ferrous (Fe(2+)) oxidation state of the sGC heme cofactor and stimulates formation of cGMP several hundred-fold. Oxidation of the sGC heme to the ferric (Fe(3+)) state desensitizes the enzyme to NO. The heme-oxidized state of sGC has emerged as a potential therapeutic target in the treatment of cardiovascular disease. Here, we investigate the molecular mechanism of NO desensitization and find that sGC undergoes a reductive nitrosylation reaction that is coupled to the S-nitrosation of sGC cysteines. We further characterize the kinetics of NO desensitization and find that heme-assisted nitrosothiol formation of ?1Cys-78 and ?1Cys-122 causes the NO desensitization of ferric sGC. Finally, we provide evidence that the mechanism of reductive nitrosylation is gated by a conformational change of the protein. These results yield insights into the function and dysfunction of sGC in cardiovascular disease.

    View details for DOI 10.1074/jbc.M112.393892

    View details for Web of Science ID 000312501600061

    View details for PubMedID 23093402

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