Hui Feng, M.D./Ph.D.
M.D.: Beijing Medical University, Beijing, China, Preventative Medicine; Ph.D.: University of Georgia, Athens, GA, Cellular Biology.
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/MYCN-driven tumor initiation 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 of 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’s laboratory focuses on identifying novel “intravasation genes” that promote the intravasation of MYC–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’s 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 role 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.
- National Cancer Institute
- American Cancer Society
- National Science Foundation
- St. Baldrick Foundation
- Mary Kay Ash Foundation
- Leukemia Research Foundation
- Karin Grunebaum Cancer Research Foundation
- Boston University
- Hui Feng, M.D., Ph.D. to Present at 10th International Conference on Zebrafish Development and Genetics
Shen N#, Korm S#, Karantanos T, Li D, Zhang X, Ritou E, Xu H, Lam A, English J, Zong WX, Liu, CT, Shirihai O, Feng H. DLST-dependence dictates metabolic heterogeneity in TCA-cycle usage among triple-negative breast cancer. 2021. Communications Biology. Accepted.
Anderson NM, Qin X, Finan JM, Lam A, Athoe J, Missiaen R, Skuli N, Kennedy A, Saini AS, Tao T , Zhu SZ, Nissim I, Look AT, Qing G, Simon MC*, Feng H*. DLST Promotes Tumor Aggression and Unveils a Vulnerability to OXPHOS Inhibition in High-Risk Neuroblastoma. Cancer Research. 2021 Sep 1;81(17):4417-4430. *Co-senior author.
Friedlander J#, Shen N#, Zeng AZ, Korm S, and Feng H. Failure to Guard: Mitochondrial Protein Quality Control in Cancer. International Journal of Molecular Sciences. 2021 Aug 2;22(15):8306. #equal contribution. PMCID: PMC8348654.
Miao KZ, Kim GY#, Meara GK#, Qin XD, and Feng H. Tipping the scales with zebrafish to understand adaptive tumor immunity. Frontiers in Cell and Developmental Biology. 2021 2021 May 20;9:660969. #equal contribution. PMCID: PMC8173129.
Zhou Y#, Lian HW#, Shen N, Korm S, Lam A, Layton O, Li D, Huiting LN, Landesman-Bollag E, Seldin DC, Fu H, Hong L*, Feng H*. The multifaceted role of protein kinase CK2 in high-risk acute lymphoblastic leukemia. Haematologica. 2020 Aug 13; haematol.2020.246918. #equal contribution, *Co-senior author. PMCID: PMC8094085
Jiang J#, Wang JC#, Yue M, Cai XI, Wang T, Su HX, Wang YW, Han M, Zhang YC, Zhu XF, Jiang P, Li P, Sun YH, Xiao WH, Feng H, Qing GL, Liu HD. Direct Phosphorylation and Stabilization of MYC by Aurora B Kinase Promote T Cell Leukemogenesis. Cancer Cell. 2020 Feb 10;37(2):200-215.e5. #equal contribution. PMCID: PMC7321798.
Qin XD, Denton WD#, Huiting LN#, Smith K, and Feng H. Unraveling the Regulatory Role of Endoplasmic-Reticulum-Associated Degradation in Tumor Immunity. Critical Reviews in Biochemistry and Molecular Biology. 2020 Aug;55(4):322-353. #equal contribution. PMCID: PMC7644137.
Qin XD#, Laroche FJF#, Peerzade SA, Lam A, Sokolov I, Feng H. In Vivo Targeting of Xenografted Human Cancer Cells with Functionalized Fluorescent Silica Nanoparticles in Zebrafish. Journal of Visualized Experiments. 2020 May 8 (159).#equal contribution. PMCID: PMC769440.
Peerzade SA, Qin XD#, Laroche F#, Palantavida S, Dokukin M, Peng B, Feng H*, Sokolov I*. Ultrabright fluorescent silica nanoparticles for in vivo targeting xenografted human tumors and cancer cells in zebrafish. Nanoscale. 2019 Nov 28;11(46):22316-22327.#equal contribution. *co-senior author. PMCID: PMC7384872
Huiting L, Samaha Y, Zhang GL, Roderick JA, Li B, Anderson NM, Wang L, Wang Y, Laroche FLF, Choi JW, Liu CT, Kelliher MA and Feng H. UFD1 Contributes to MYC-mediated Leukemia Aggressiveness through Suppression of the Proapoptotic Unfolded Protein Response. 2018 Apr 25 [Epub ahead of print]. Leukemia. PMCID: PMC6202254
Anderson NM, Mucka P, Kern J, and Feng H. The Emerging Role and Targetability of the TCA Cycle in Cancer Metabolism. 2018 Feb; 9(2):216-237. Protein & Cell. PMCID: PMC5818369.
Lian HW, Li D, Zhou Y, Landesman-Bollag E, Zhang GL, Anderson NM, Tang KC, Roderick JE, Kelliher MA, Zhang G, Seldin DC, Fu H* and Feng H*. CK2 inhibitor CX-4945 destabilizes NOTCH1 and synergizes with JQ1 against human T-acute lymphoblastic leukemic cells. Haematologica. 2017 Jan;102(1):e17-e21. *co-senior author. PMCID: PMC5210253
Anderson NM, Li D, Peng HL, Laroche FJF, Mansour MR, Gjini E, Aioub M, Helman DJ, Roderick JE, Cheng T, Harrold I, Samaha Y, Le M, Amsterdam A, Neuberg DS, Denton TT, Sanda T, Kelliher MA, Singh A, Look AT, Feng H. The TCA cycle transferase DLST is important for MYC-mediated leukemogenesis. Leukemia, 2016 30(6):1365-74. PMCID: PMC4889531
Harrold I#, Carbonneau S#, Moore B, Nguyen G, Anderson NM, Saini A, Kanki JP, Jette C, Feng H. Efficient transgenesis mediated by pigmentation rescue. Biotechniques. 2016 60(1):12-20. #These authors contributed equally to this work. PMCID: PMC4768720
Harrison N#, Laroche FJF#, Gutierrez A, Feng H. Zebrafish models of human leukemia: technological advances and mechanistic insights. Advances in Experimental Medicine and Biology. 2016; 916:335-69. # these authors contributed equally to this work. PMCID: PMC4933302
Huiting LN, Laroche F.J.F., Feng H. The Zebrafish as a Tool for Cancer Drug Discovery. Austin Journal of Pharmacology and Therapeutics. 2015 May;3(2):1069. PMCID: PMC4731041.
Anderson NM#, Harrold I#, Mansour M, Sanda T, McKeown M, Nagykary N, Bradner JE, Zhang GL, Look AT*, Feng H*. 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. 2014 28(5):1145-8. # these authors contributed equally to this work. *co-senior author. PMCID: PMC4013222.
Zhu SZ, Lee JS, Guo F, Shin J, Perez-Atayde AR, Kutok JL, Rodig SJ, Neuberg DS, Helman DJ, 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. PMCID: PMC3315700.12.
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: .
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., Kipreos E.T. Preventing DNA re-replication—divergent safeguards in yeast and metazoan. Cell Cycle. 2003 Sep-Oct;2(5):431-4. Review. PMID: 12963835.
Zhong W, Feng H, Santiago FE, Kipreos ET. CUL-4 ubiquitin ligase maintains genome stability by restraining DNA-replication licensing. Nature. 2003 Jun 19;423(6942):885-9.
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.
Office: The Cancer Center, Boston University School of Medicine, 72 East Concord Street, K-712A, Boston, MA 02118
Lab Phone: 617-358-4636