The overarching goal of my research program is to gain an understanding of the molecular mechanisms that govern stem cell potency and how dysregulation of these mechanisms can contribute to disease onset and progression, including oncogenesis. My laboratory employs genetic, genomic, and single-cell analysis approaches in murine systems to address these fundamental questions, and, in parallel, utilizes human induced pluripotent cells and patient samples to translate findings into human systems. Using these approaches we have identified novel pathways underlying the somatic stem cell self-renewal and the ontogeny of hematopoietic and gastrointestinal cancers. These pathways are subsequently being assessed as potential points for therapeutic intervention in cancers and diseases of regenerative failure. We have also begun to unravel the hierarchical structure of the intestinal stem cell compartment with the ultimate goal of understanding how perturbations in this hierarchy contribute to disease states, including cancer, chronic inflammation, and regeneration in response to acute injuries such as ischemia or radiation damage.
Ning Li, M.D., Postdoctoral Fellow
Dong-Hun Woo, Ph.D., Postdoctoral Fellow
Angela Ddamba, Research Specialist
Ryan Cedeno, Graduate Student
Maryam Yousefi, Graduate Student (HHMI International Fellow)
Carla Hoge, Undergraduate (UPenn Vagelos Scholar)
Wang, Shan; Li, Ning; Yousefi, Maryam; Nakauka-Ddamba, Angela; Li, Fan; Parada, Kimberly; Rao, Shilpa; Minuesa, Gerard; Katz, Yarden; Gregory, Brian D; Kharas, Michael G; Yu, Zhengquan; Lengner, Christopher J.: Transformation of the intestinal epithelium by the MSI2 RNA-binding protein. Nature communications 6: 6517, 2015.
Park, Sun-Mi; Gonen, Mithat; Vu, Ly; Minuesa, Gerard; Tivnan, Patrick; Barlowe, Trevor S; Taggart, James; Lu, Yuheng; Deering, Raquel P; Hacohen, Nir; Figueroa, Maria E; Paietta, Elisabeth; Fernandez, Hugo F; Tallman, Martin S; Melnick, Ari; Levine, Ross; Leslie, Christina; Lengner, Christopher J; Kharas, Michael G.: Musashi2 sustains the mixed-lineage leukemia-driven stem cell regulatory program. Journal of Clinical Investigation 125(3): 1286-98, Mar 2 2015.
Li, Ning; Yousefi, Maryam; Nakauka-Ddamba, Angela; Jain, Rajan; Tobias, John; Epstein, Jonathan A; Jensen, Shane T; Lengner, Christopher J.: Single-cell analysis of proxy reporter allele-marked epithelial cells establishes intestinal stem cell hierarchy. Stem Cell Reports 3(5): 876-91, Nov 11 2014.
Park, Sun-Mi; Deering, Raquel P; Lu, Yuheng; Tivnan, Patrick; Lianoglou, Steve; Al-Shahrour, Fatima; Ebert, Benjamin L; Hacohen, Nir; Leslie, Christina; Daley, George Q; Lengner, Christopher J; Kharas, Michael G.: Musashi-2 controls cell fate, lineage bias, and TGF-beta signaling in HSCs. Journal of Experimental Medicine 211(1): 71-87, Jan 13 2014.
Lengner Christopher J, Gimelbrant Alexander A, Erwin Jennifer A, Cheng Albert Wu, Guenther Matthew G, Welstead G Grant, Alagappan Raaji, Frampton Garrett M, Xu Ping, Muffat Julien, Santagata Sandro, Powers Doug, Barrett C Brent, Young Richard A, Lee Jeannie T, Jaenisch Rudolf, Mitalipova Maisam: Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations. Cell 141(5): 872-83, May 2010.
Kharas Michael G*, Lengner Christopher J*, Al-Shahrour Fatima, Bullinger Lars, Ball Brian, Zaidi Samir, Morgan Kelly, Tam Winnie, Paktinat Mahnaz, Okabe Rachel, Gozo Maricel, Einhorn William, Lane Steven W, Scholl Claudia, Fröhling Stefan, Fleming Mark, Ebert Benjamin L, Gilliland D Gary, Jaenisch Rudolf, Daley George Q
*equally contributing authors: Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia. Nature medicine 16(8): 903-8, Aug 2010.
Hanna Jacob, Saha Krishanu, Pando Bernardo, van Zon Jeroen, Lengner Christopher J, Creyghton Menno P, van Oudenaarden Alexander, Jaenisch Rudolf: Direct cell reprogramming is a stochastic process amenable to acceleration. Nature 462(7273): 595-601, Dec 2009.
Markoulaki Styliani, Hanna Jacob, Beard Caroline, Carey Bryce W, Cheng Albert W, Lengner Christopher J, Dausman Jessica A, Fu Dongdong, Gao Qing, Wu Su, Cassady John P, Jaenisch Rudolf: Transgenic mice with defined combinations of drug-inducible reprogramming factors. Nature biotechnology 27(2): 169-71, Feb 2009.
Wernig Marius*, Lengner Christopher J*, Hanna Jacob, Lodato Michael A, Steine Eveline, Foreman Ruth, Staerk Judith, Markoulaki Styliani, Jaenisch Rudolf
*equally contributing authors: A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types. Nature biotechnology 26(8): 916-24, Aug 2008.
Lengner Christopher J, Camargo Fernando D, Hochedlinger Konrad, Welstead G Grant, Zaidi Samir, Gokhale Sumita, Scholer Hans R, Tomilin Alexey, Jaenisch Rudolf: Oct4 expression is not required for mouse somatic stem cell self-renewal. Cell stem cell 1(4): 403-15, Oct 2007.
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Last updated: 11/18/2015
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