Professional Education


  • Doctor of Science, University of Florida (2019)
  • Bachelor (Undeclared), Middle School attached to HUST (2012)
  • Master of Public Health, University of Florida (2015)
  • Ph.D., University of Florida, Cancer Biology and Pharmacology (2019)
  • M.P.H., University of Florida, Epidemiology (2015)
  • M.D., Huanzhong University of Science and Technology, Medicine (2012)

Stanford Advisors


Current Research and Scholarly Interests


1. To investigate the role of p53 in regulating the regression of lung adenocarcinoma and tumor microenvironment.
2. To determine synthetic lethal partner for p53 mutations in the context of lung adenocarcinoma.

All Publications


  • A novel proteotoxic combination therapy for EGFR+ and HER2+cancers ONCOGENE Wang, M., Ferreira, R. B., Law, M. E., Davis, B. J., Yaaghubi, E., Ghilardi, A. F., Sharma, A., Avery, B. A., Rodriguez, E., Chiang, C., Narayan, S., Heldermon, C. D., Castellano, R. K., Law, B. K. 2019; 38 (22): 4264–82

    Abstract

    While HER2 and EGFR are overexpressed in breast cancers and multiple other types of tumors, the use of EGFR and/or HER2 inhibitors have failed to cure many cancer patients, largely because cancers acquire resistance to HER2/EGFR-specific drugs. Cancers that overexpress the HER-family proteins EGFR, HER2, and HER3 are uniquely sensitive to agents that disrupt HER2 and EGFR protein folding. We previously showed that disruption of disulfide bond formation by Disulfide Disrupting Agents (DDAs) kills HER2/EGFR overexpressing cells through multiple mechanisms. Herein, we show that interference with proline isomerization in HER2/EGFR overexpressing cells also induces cancer cell death. The peptidyl-prolyl isomerase inhibitor Cyclosporine A (CsA) selectively kills EGFR+ or HER2+ breast cancer cells in vitro by activating caspase-dependent apoptotic pathways. Further, CsA synergizes with the DDA tcyDTDO to kill HER2/EGFR overexpressing cells in vitro and the two agents cooperate to kill HER2+ tumors in vivo. There is a critical need for novel strategies to target HER2+ and EGFR+ cancers that are resistant to currently available mechanism-based agents. Drugs that target HER2/EGFR protein folding, including DDAs and CsA, have the potential to kill cancers that overexpress EGFR or HER2 through the induction of proteostatic synthetic lethality.

    View details for DOI 10.1038/s41388-019-0717-6

    View details for Web of Science ID 000469339100005

    View details for PubMedID 30718919

  • The unfolded protein response as a target for anticancer therapeutics CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY Wang, M., Law, M. E., Castellano, R. K., Law, B. K. 2018; 127: 66–79

    Abstract

    The endoplasmic reticulum (ER) is an essential organelle in eukaryotic cells, responsible for protein synthesis, folding, sorting, and transportation. ER stress is initiated when the unfolded or misfolded protein load exceeds the capacity of the ER to properly fold protein. Tumor microenvironmental conditions, such as nutrient deprivation, hypoxia, and oxidative stress perturb protein folding and trigger chronic ER stress. Cancer cells can tolerate mild ER stress, however, persistent and severe ER stress kills cancer cells by inducing their autophagy, apoptosis, necroptosis, or immunogenic cell death. Based on this rationale, many drugs have been developed for triggering irremediable ER stress in cancer cells by targeting various processes in the secretory pathway. This review discusses the mechanisms of protein targeting to the ER, the key signaling cassettes that are involved in the ER stress response, and their correlation with cancer formation and progression. Importantly, this review discusses current experimental and FDA approved anti-cancer drugs that induce ER stress, and emerging targets within the secretory pathway for the development of new anticancer drugs.

    View details for DOI 10.1016/j.critrevonc.2018.05.003

    View details for Web of Science ID 000437044500008

    View details for PubMedID 29891114

  • Disulfide bond disrupting agents activate the unfolded protein response in EGFR- and HER2-positive breast tumor cells ONCOTARGET Ferreira, R. B., Wang, M., Law, M. E., Davis, B. J., Bartley, A. N., Higgins, P. J., Kilberg, M. S., Santostefano, K. E., Terada, N., Heldermon, C. D., Castellano, R. K., Law, B. K. 2017; 8 (17): 28971–89

    Abstract

    Many breast cancer deaths result from tumors acquiring resistance to available therapies. Thus, new therapeutic agents are needed for targeting drug-resistant breast cancers. Drug-refractory breast cancers include HER2+ tumors that have acquired resistance to HER2-targeted antibodies and kinase inhibitors, and "Triple-Negative" Breast Cancers (TNBCs) that lack the therapeutic targets Estrogen Receptor, Progesterone Receptor, and HER2. A significant fraction of TNBCs overexpress the HER2 family member Epidermal Growth Factor Receptor (EGFR). Thus agents that selectively kill EGFR+ and HER2+ tumors would provide new options for breast cancer therapy. We previously identified a class of compounds we termed Disulfide bond Disrupting Agents (DDAs) that selectively kill EGFR+ and HER2+ breast cancer cells in vitro and blocked the growth of HER2+ breast tumors in an animal model. DDA-dependent cytotoxicity was found to correlate with downregulation of HER1-3 and Akt dephosphorylation. Here we demonstrate that DDAs activate the Unfolded Protein Response (UPR) and that this plays a role in their ability to kill EGFR+ and HER2+ cancer cells. The use of breast cancer cell lines ectopically expressing EGFR or HER2 and pharmacological probes of UPR revealed all three DDA responses: HER1-3 downregulation, Akt dephosphorylation, and UPR activation, contribute to DDA-mediated cytotoxicity. Significantly, EGFR overexpression potentiates each of these responses. Combination studies with DDAs suggest that they may be complementary with EGFR/HER2-specific receptor tyrosine kinase inhibitors and mTORC1 inhibitors to overcome drug resistance.

    View details for DOI 10.18632/oncotarget.15952

    View details for Web of Science ID 000400050000113

    View details for PubMedID 28423644

    View details for PubMedCentralID PMC5438706