Hui Feng, M.D./Ph.D.
M.D.: Beijing Medical University, Beijing, China, Preventative Medicine; Ph.D.: University of Georgia, Athens, GA, Cellular Biology.
Cancer Research: Dr. Feng is Director of the Laboratory of Zebrafish Genetics and Cancer Therapeutics. Dr. Feng’s research interests focus on identifying novel genes and pathways that are essential for MYC-related tumor transformation and progression, particularly for T-Lymphoblastic Lymphoma/Leukemia, Breast Cancer, and Neuroblastoma. The research strategy of Dr. Feng’s research is to combine the analysis of human cancer genomic databases with the genetic and imaging capacities of the zebrafish system.
Cancer takes the lives of millions each year and over 90% of cancer-related deaths result from tumor metastasis. Therefore; there is an urgent need to develop novel strategies that can block tumor metastasis and kill cancer cells efficiently and specifically. MYC, aptly referred to by Gerard Evan as the oncogene (cancer-causing gene) from hell, is aberrantly activated in nearly all human cancers, including leukemias, lymphomas, neuroblastoma and carcinomas. Cancers with aberrant MYCactivity are often aggressive, rapidly spreading to distant tissues. These facts underscore the need to improve understanding of the regulatory molecules involved with MYC-induced tumor initiation and progression, thus allowing the researchers to discover and exploit the vulnerabilities of the cancers, in order to develop novel and effective drugs targeting MYC-related cancers.
The zebrafish offers many unique advantages as a cancer model: easy monitoring of tumor development in vivo, due to its transparency and the ability to differentially fluorochrome-label tumor cells and vasculature; a high degree of genetic similarities with humans; simple techniques for functional studies of candidate genes identified through ongoing human genomic analysis; and the feasibility of conducting genetic and chemical screens to dissect the molecular pathways of tumorigenesis and identify promising lead compounds. The research in Feng laboratory uses the zebrafish model in combination with human cell line and patient sample analyses,
1) to determine the molecular mechanisms underlying tumor cell intravasation and tumor progression.
2) to identify genes and pathways that, when inactivated, delay the initiation and progression of MYC-related cancers.
3) to test the identified genes’ therapeutic potential in treating MYC-related cancers and to characterize their molecular relevance to MYC.
One major project in Feng laboratory is to dissect molecular pathways that regulate the initial step of tumor metastasis – intravasation – the entry of tumor cells into vascular and/or lymphatic vessels. Improved understanding about tumor cell intravasation is the key for future therapeutic developments to block the spread of tumor cells from their primary site. Through interrogating human cancer genomic information with the imaging and genetic capacities of the zebrafish system, researchers in Feng laboratory focuses on identifying novel “intravasation genes” that promote the intravasation ofMYC-driven tumor cells. Using this combined approach, the Feng laboratory has successfully identified multiple promising genes. Genes identified through these studies should represent promising targets for therapeutic intervention to block MYC-associated metastasis. As the next step of the research, their therapeutic potential will be evaluated using human cancer cell lines.
The second major project in Feng laboratory is to exploit the genetic capacity of the zebrafish system to identify genes that, when inactivated, can inhibit or delay tumor development. Researchers in Feng laboratory have identified a gene critical for energy production and macromolecule synthesis – ~50% reduction of this gene delayed Myc-induced T-cell leukemia but did not influence fish development. This finding is consistent with MYC’s important roles in cancer metabolism.
The long-term goal of Dr. Feng’s research is to discover novel molecular therapies to target critical components of MYC-driven oncogenic pathways, thus providing treatment alternatives that are more specific and less toxic.
- Howard-Temin Pathway to Independence Award (R00), NCI.
- Department of Pharmacology & Experimental Therapeutics and Cancer Center, BUSM.
- Karin Grunebaum Junior Faculty Fellowship.
- Ralph Edwards Career Development Professorship
- UROP, SURP, RISE, Boston University.
Alejandro Gutierrez, Hui Feng, Donna S. Neuberg, Oscar Calzada, Yi Zhou, David M. Langenau, and A. Thomas Look. Loss of function p53 mutations do not accelerate the onset of Myc-induced T-ALL in the zebrafish. 2014. Brit. J. Heamatol. Accepted)
Nicole M. Anderson¶, Itrat Harrold¶, Marc R. Mansour, Takaomi Sanda, Michael McKeown, Nicholas Nagykary, James E. Bradner, Guang Lan Zhang, A.Thomas Look and Hui Feng. 2013. BCL2-specific inhibitor ABT-199 synergizes strongly with cytarabine against the early immature LOUCY cell line but not more differentiated T-ALL cell lines. Leukemia (Accepted). ¶equal contribution.
Blackburn JS, Liu S, Raiser DM, Martinez SA, Feng H, Meeker ND, Gentry J, Neuberg D, Look AT, Ramaswamy S, Bernards A, Trede NS, Langenau DM. Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency. Leukemia. 2012 Apr 27. doi: 10.1038/leu.2012.116. [Epub ahead of print]. Abstract: .
Zhu S, Lee JS, Guo F, Shin J, Perez-Atayde AR, Kutok JL, Rodig SJ, Neuberg DS, Helman D, Feng H, Stewart RA, Wang W, George RE, Kanki JP, Look AT. Activated ALK collaborates with MYCN in neuroblastoma pathogenesis. Cancer Cell. 2012 Mar 20;21(3):362-73. Abstract: .
Gutierrez A, Grebliunaite R, Feng H, Kozakewich E, Zhu S, Guo F, Payne E, Mansour M, Dahlberg SE, Neuberg DS, den Hertog J, Prochownik EV, Testa JR, Harris M, Kanki JP, Look AT. Pten mediates Myc oncogene dependence in a conditional zebrafish model of T cell acute lymphoblastic leukemia. J Exp Med. 2011 Aug 1;208(8):1595-603. PMC3149218. Full Article: .
Feng H, Stachura DL, White RM, Gutierrez A, Zhang L, Sanda T, Jette CA, Testa JR, Neuberg DS, Langenau DM, Kutok JL, Zon LI, Traver D, Fleming MD, Kanki JP, Look AT.T-lymphoblastic lymphoma cells express high levels of BCL2, S1P1, and ICAM1, leading to a blockade of tumor cell intravasation. Cancer Cell. 2010 Oct 19;18(4):353-66. PMC3003429. Full article: .
Bosu DR, Feng H, Min K, Kim Y, Wallenfang MR, Kipreos ET.C. elegans CAND-1 regulates cullin neddylation, cell proliferation and morphogenesis in specific tissues. Dev Biol. 2010 Oct 1;346(1):113-26. Epub 2010 Jul 24. PMC2955628. Full article: .
Freeman JL, Ceol C, Feng H, Langenau DM, Belair C, Stern HM, Song A, Paw BH, Look AT, Zhou Y, Zon LI, Lee C. Construction and application of a zebrafish array comparative genomic hybridization platform. Genes Chromosomes Cancer . 2009 Feb;48(2):155-70. PMC2605212. Full article:.
Feng H, Langenau DM, Madge JA, Quinkertz A, Gutierrez A, Neuberg DS, Kanki JP, Look AT. Heat-shock induction of T-cell lymphoma/leukaemia in conditional Cre/lox-regulated transgenic zebrafish. Br J Haematol. 2007 Jul;138(2):169-75. Abstract: .
Kim J, Feng H, Kipreos ET. C. elegans CUL-4 prevents rereplication by promoting the nuclear export of CDC-6 via a CKI-1-dependent pathway. Curr Biol. 2007 Jun 5;17(11):966-72. PMC1945017. Full Article: .
Langenau DM, Feng H, Berghmans S, Kanki JP, Kutok JL, Look AT.Cre/lox-regulated transgenic zebrafish model with conditional myc-induced T cell acute lymphoblastic leukemia. Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):6068-73. Epub 2005 Apr 12. PMC1087915. Full article: .
Feng H, Zhong W, Punkosdy G, Gu S, Zhou L, Seabolt EK, Kipreos ET.CUL-2 is required for the G1-to-S-phase transition and mitotic chromosome condensation in Caenorhabditis elegans. Nat Cell Biol. 1999 Dec;1(8):486-92. Abstract: .
Office: The Cancer Center, Boston University School of Medicine, 72 East Concord Street, K-712A, Boston, MA 02118
Lab Phone: 617-358-4636