Photo of Rizwan Haq,  MD, PhD

Rizwan Haq, MD, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute


rizwan_haq@dfci.harvard.edu

Rizwan Haq, MD, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Assistant Professor, Medicine, Harvard Medical School
  • Principal Investigator, Medical Oncology, Dana-Farber Cancer Institute
  • Associate Member, Cancer Biology, Broad Institute of MIT and Harvard

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our lab is interested in why current generation treatments for melanoma fail, so that we can design rational approaches to improve them. This research falls into two major categories:

1. Targeted therapies, such as BRAF inhibitors. We have demonstrated that BRAF inhibitors not only induce cytotoxic pathways in melanoma cells, but also induce pathways that paradoxically promote survival (for example, Haq et al, Cancer Cell (2013)). We are characterizing these “adaptive resistance” pathways at a deep molecular level, so we can develop combinatorial approaches to overcome this resistance. Our comprehensive surveys suggest that this form of resistance is ubiquitous in melanoma and in virtually all other cancer types.

2. Immunotherapies. We have recently developed new models to evaluate resistance to immunotherapy. Using these approaches, we have designed comprehensive screens to identify mechanisms of innate resistance to immunotherapies such as PD-1/PD-L1 inhibitors and CTLA-4 checkpoint inhibitors. Characterizing candidate resistance pathways at a molecular level will lead, it is hoped, to the development of strategies to improve these treatments using combinations of small molecules and immunotherapies.

Publications

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  • Gee MS, Ghazani AA, Haq R, Wargo JA, Sebas M, Sullivan RJ, Lee H, Weissleder R. Point of care assessment of melanoma tumor signaling and metastatic burden from μNMR analysis of tumor fine needle aspirates and peripheral blood. 2016. PubMed
  • Lauss M, Haq R, Cirenajwis H, Phung B, Harbst K, Staaf J, Rosengren F, Holm K, Aine M, Jirström K, Borg Å, Busch C, Geisler J, Lønning PE, Ringnér M, Howlin J, Fisher DE, Jönsson G. Genome-Wide DNA Methylation Analysis in Melanoma Reveals the Importance of CpG Methylation in MITF Regulation. J Invest Dermatol 2015. PubMed
  • Haq R, Flaherty K. The melanoma metastasis X-factor. Pigment Cell Melanoma Res 2014; 27:698. PubMed
  • Konieczkowski DJ, Johannessen CM, Abudayyeh O, Kim JW, Cooper ZA, Piris A, Frederick DT, Barzily-Rokni M, Straussman R, Haq R, Fisher DE, Mesirov JP, Hahn WC, Flaherty KT, Wargo JA, Tamayo P, Garraway LA. A melanoma cell state distinction influences sensitivity to MAPK pathway inhibitors. 2014. PubMed
  • Haq R, Fisher DE, Widlund HR. Molecular pathways: BRAF induces bioenergetic adaptation by attenuating oxidative phosphorylation. Clin Cancer Res 2014. PubMed
  • Haq R. Metabolic dysregulation in melanoma: cause or consequence? 2014; 4:390-1. PubMed
  • Frederick DT, Salas Fragomeni RA, Schalck A, Ferreiro-Neira I, Hoff T, Cooper ZA, Haq R, Panka DJ, Kwong LN, Davies MA, Cusack JC, Flaherty KT, Fisher DE, Mier JW, Wargo JA, Sullivan RJ. Clinical profiling of BCL-2 family members in the setting of BRAF inhibition offers a rationale for targeting de novo resistance using BH3 mimetics. PLoS ONE 2014; 9:e101286. PubMed
  • Haq R, Fisher DE. Improving apoptotic responses to targeted therapy. 2013; 4:1331. PubMed
  • Haq R, Fisher DE. Targeting melanoma by small molecules: challenges ahead. Pigment Cell Melanoma Res 2013. PubMed
  • Haq R, Shoag J, Andreu-Perez P, Yokoyama S, Edelman H, Rowe GC, Frederick DT, Hurley AD, Nellore A, Kung AL, Wargo JA, Song JS, Fisher DE, Arany Z, Widlund HR. Oncogenic BRAF regulates oxidative metabolism via PGC1α and MITF. Cancer Cell 2013; 23:302-15. PubMed
  • Haq R, Yokoyama S, Hawryluk EB, Jönsson GB, Frederick DT, McHenry K, Porter D, Tran TN, Love KT, Langer R, Anderson DG, Garraway LA, Duncan LM, Morton DL, Hoon DS, Wargo JA, Song JS, Fisher DE. BCL2A1 is a lineage-specific antiapoptotic melanoma oncogene that confers resistance to BRAF inhibition. Proc Natl Acad Sci U S A 2013; 110:4321-6. PubMed
  • Shoag J, Haq R, Zhang M, Liu L, Rowe GC, Jiang A, Koulisis N, Farrel C, Amos CI, Wei Q, Lee JE, Zhang J, Kupper TS, Qureshi AA, Cui R, Han J, Fisher DE, Arany Z. PGC-1 coactivators regulate MITF and the tanning response. Mol Cell 2013; 49:145-57. PubMed
  • Li J, Song JS, Bell RJ, Tran TN, Haq R, Liu H, Love KT, Langer R, Anderson DG, Larue L, Fisher DE. YY1 regulates melanocyte development and function by cooperating with MITF. PLoS Genet. 2012; 8:e1002688. PubMed
  • Yokoyama S, Woods SL, Boyle GM, Aoude LG, MacGregor S, Zismann V, Gartside M, Cust AE, Haq R, Harland M, Taylor JC, Duffy DL, Holohan K, Dutton-Regester K, Palmer JM, Bonazzi V, Stark MS, Symmons J, Law MH, Schmidt C, Lanagan C, O'Connor L, Holland EA, Schmid H, Maskiell JA, Jetann J, Ferguson M, Jenkins MA, Kefford RF, Giles GG, Armstrong BK, Aitken JF, Hopper JL, Whiteman DC, Pharoah PD, Easton DF, Dunning AM, Newton-Bishop JA, Montgomery GW, Martin NG, Mann GJ, Bishop DT, Tsao H, Trent JM, Fisher DE, Hayward NK, Brown KM. A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma. Nature 2011; 480:99-103. PubMed
  • Haq R, Fisher DE. Biology and clinical relevance of the micropthalmia family of transcription factors in human cancer. J Clin Oncol 2011; 29:3474-82. PubMed
  • McGill GG, Haq R, Nishimura EK, Fisher DE. c-Met expression is regulated by Mitf in the melanocyte lineage. J Biol Chem 2006; 281:10365-73. PubMed
  • Haq R, Brenton JD, Takahashi M, Finan D, Finkielsztein A, Damaraju S, Rottapel R, Zanke B. Constitutive p38HOG mitogen-activated protein kinase activation induces permanent cell cycle arrest and senescence. Cancer Res 2002; 62:5076-82. PubMed
  • Ho JM, Nguyen MH, Dierov JK, Badger KM, Beattie BK, Tartaro P, Haq R, Zanke BW, Carroll MP, Barber DL. TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways. Blood 2002; 100:1438-48. PubMed
  • Haq R, Halupa A, Beattie BK, Mason JM, Zanke BW, Barber DL. Regulation of erythropoietin-induced STAT serine phosphorylation by distinct mitogen-activated protein kinases. J Biol Chem 2002; 277:17359-66. PubMed
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