Wang N*, Li N*, Yousefi M, Nakauka-Ddamba A, Li F, Parada K, Rao S, Minuesa G, Katz Y, Gregory BD, Kharas MG, Yu Z, Lengner CJ. “Transformation of the intestinal epithelium by the MSI2 RNA binding protein.” Nature Communications, 2015 In Press, PMCID in process. doi:10.1038/ncomms7517 *Authors contributed equally
Park SM, Gönen M, Vu L, Minuesa G, Tivnan P, Barlowe TS, Taggart J, Lu Y, Deering RP, Hacohen N, Figueroa ME, Paietta E, Fernandez HF, Tallman MS, Melnick A, Levine R, Leslie C, Lengner CJ, Kharas MG. “Musashi2 sustains the mixed-lineage leukemia-driven stem cell regulatory program.” J. Clinical Investigation, 2015 Feb 9. pii: 78440. doi: 10.1172/JCI78440.
Li N, Yousefi M, Nakauka-Ddamba A, Jain R, Tobias J, Epstein JA, Jensen S, Lengner CJ. “Single cell analysis of proxy reporter allele-marked epithelial cells establishes intestinal stem cell hierarchy.” Stem Cell Reports, 2014 Nov 11;3(5):876-91. PMCID: PMC4235148
Katz Y, Li F, Lambert NJ, Sokol ES, Tam WL, Cheng AW, Airoldi EM, Lengner CJ, Gupta PB, Yu Z, Jaenisch R, Burge CB. “Musashi proteins are post-transcriptinoal regulators of the epithelial-luminal cell state.” Elife, 2014 Nov 7;3:e03915. doi: 10.7554/eLife.03915. PMID: 25380226. PMCID: In Process
Yildirim O, Hung JH, Cedeno R, Weng Z, Lengner CJ*, Rando OJ*. “A system for
genome-wide histone variant dynamics in ES cells reveals dynamic Macro-H2A replacement at promoters.” PLoS Genetics, 2014 Aug 7;10(8):e1004515, 2014. PMCID: PMC4125097 *Corresponding authors
Park SM, Deering RP, Lu Y, Tivnan P, Lianoglou S, Al-Shahrour F, Ebert BL, Leslie C, Daley GQ, Lengner CJ, Kharas MG. "Msi2 controls self-renewal, lineage restriction and TGF-β signaling in HSCs." Journal of Experimental Medicine, 2014 Jan 13;211(1):71-87. doi: 10.1084/jem.20130736. Epub 2014 Jan 6.
Liu JC, Lengner CJ, Gaur T, Lou Y, Hussain S, Jones MD, Borodic B, Colby JL,
Steinman HA, van Wijnen AJ, Stein JL, Jones SN, Stein GS, Lian JB. “Runx2 protein
expression utilizes the Runx2 P1 promoter to establish osteoprogenitor cell number for normal bone formation." J Biol Chem. 2011 Aug 26;286(34):30057-70.
Kharas MG*, Lengner CJ*, Al-Shahrour F, Bullinger L, Ball B, Zaidi S, Morgan K, Tam W, Paktinat M, Okabe R, Gozo M, Scholl C, Frohling S, Fleming M, Ebert BL, Gilliland DG, Jaenisch R, Daley GQ. “Musashi-2 promotes hematopoietic stem cell proliferation and accelerates myeloid leukemogenesis.” Nature Medicine 2010 Aug;16(8):903-8. Epub 2010 Jul 8. *Authors contributed equally (Faculty of 1000 Must Read)
Lengner CJ*, Gimelbrant AA*, Erwin JA, Cheng AW, Guenther MG, Welstead GG, Alagappan R, Frampton GM, Xu P, Muffat J, Santagata S, Powers D, Barrett CB, Young RA, Lee JT, Jaenisch R, Mitalipova M. "Derivation of pre-X inactivation human embryonic stem cells under physiological oxygen concentrations." Cell. 2010 May 28;141(5):872-83. Epub 2010 May 13. (Faculty of 1000 Exceptional)
Lengner CJ. “iPS cell technology and regenerative medicine.” Ann N Y Acad Sci. 2010 Mar;1192(1):38-44
Hanna J*, Saha K*, Pando B, van Zon J, Lengner, CJ, Creyghton MP, van
Oudenaarden A, and Jaenisch R. “Direct reprogramming is a stochastic process amenable to cell division rate dependent and independent acceleration” Nature. 2009 Dec 3;462(7273):595-601. Epub 2009 Nov 8. (Faculty of 1000 Recommended)
Wernig M*, Lengner CJ*, Hanna J, Lodato MA, Steine E, Foreman R, Staerk J, Markoulaki S, and Jaenisch R. “A drug-inducible transgenic system for direct reprogramming of multiple somatic cell types”. Nature Biotechnology. 2008 Aug;26(8):916-24. *Authors contributed equally (Faculty of 1000 Must Read)
Hanna J, Markoulaki S, Schorderet P, Carey BW, Beard C, Wernig M, Creyghton MP, Steine EJ, Cassady JP, Foreman R, Lengner CJ, Dausman JA, Jaenisch R. “Direct
reprogramming of terminally differentiated mature B lymphocytes to pluripotency.” Cell. 2008 Apr 18;133(2):250-64. (Faculty of 1000 Must Read)
Lengner CJ, Welstead GG, Jaenisch R. “The pluripotency regulator Oct4: A role in somatic stem cells?” Cell Cycle. 2008 Jan14; 7(6).
Lengner CJ, Camargo FD, Hochedlinger K, Welstead GG, Zaidi S Gokhale S, Scholer HR, Tomilin A, and Jaenisch R.“Oct4 expression is not required for mouse somatic stem cell self-renewal.” Cell Stem Cell. 2007 Oct; 1(4). (Faculty of 1000 Must Read)
Lengner CJ*, Steinman HA*, Gagnon J, Smith TW, Henderson JE, Kream BE, Stein GS, Lian JB, Jones SN. “Osteoblast differentiation and skeletal development are regulated by Mdm2-p53 signaling.” Journal of Cell Biology. 2006 Mar 13; 172(6): 909-21.
Lengner CJ, Hassan MQ, Serra RW, Lepper C, van Wijnen AJ, Stein JL, Stein GS, Lian JB. “Nkx3.2-mediated repression of Runx2 promotes chondrogenic differentiation.” Journal of Biological Chemistry. 2005 Sep 30; 280(39): 33132-40.
Lengner CJ, Lepper C, van Wijnen AJ, Stein JL, Stein GS, Lian JB. “Primary mouse
embryonic fibroblasts: A model of mesenchymal cartilage formation.” Journal of Cellular Physiology. 2004 Sep; (3): 327-33.
Lengner CJ, Drissi H, Choi JY, van Wijnen AJ, Stein JL, Stein GS, Lian JB. “Activation of the bone-related Runx2/Cbfa1 promoter in mesenchymal condensations and developing chondrocytes of the axial skeleton.” Mechanisms of Development. 2002 Jun; 114(1-2): 167-70.
*Denotes equal author contribution
Chris Lengner, Ph.D. - Principal Investigator
Chris received his B.S. in Biotechnology from the Worcester Polytechnic Institute and his Ph.D. from the University of Massachusetts Medical School. During this time, he became interested in stem cell biology while studying the molecular mechanisms underlying cell fate determination in developing skeletal tissues and osteosarcoma. Chris continued to pursue his interest in stem cell biology as a Ruth L. Kirschstein Postdoctoral Fellow with Rudolf Jaensich at the Whitehead Institute at MIT in Cambridge, MA. At the Whitehead, Chris continued to study somatic stem cells using murine genetic model systems, and also developed an interest in pluripotency of embryonic stem cells and the generation of induced pluripotent stem cells. Upon joining the faculty of the University of Pennsylvania, Chris’ research has focused on somatic stem cells of the intestinal epithelium, how their self-renewal is regulated, and how molecular mechanisms governing self-renewal go wrong in diseases such as cancer.
Outside of the lab Chris enjoys hiking, skiing, reading, traveling, and fine American IPAs.
Angela Ddamba, BA - Research Specialist
Angela came to work in the lab after graduating from the University of Pennsylvania with a degree in Biology and African Studies. As research specialist, is responsible for the daily running of the lab and its activities, and for maintaining our mouse colony.
On the research front, Angela is interested in the role Msi proteins play in oncogenic transformation and stem cell maintenance. Previous studies in the lab have established that Msi proteins act as potent oncogenes to drive the proliferative expansion of intestinal stem cells in a cell-autonomous manner. However, we have also recently observed that Msi2 binds to several messenger RNAs (mRNA) encoding regulators of the intestinal microbiota and immune response (for example, Reg3gamma, an antibacterial lectin secreted from intestinal epithelial cells responsible for maintaining a barrier between the epithelium and the luminal microbiota). Angela’s project in the lab is therefore focused on addressing the hypothesis that the oncogenic effects of Msi overexpression in colorectal cancer are not solely epithelial cell-autonomous, but are also due to a second, non-cell autonomous role in promotion of inflammation through loss of epithelial barrier function and inappropriate translocation of the luminal microbiota through the epithelial barrier.
Outside of work, Angela loves keeping fit, reading literature from all over the world, keeping up with health issues, and trying out new recipes.
Ryan Cedeno, B.S. - Graduate Assistant
Ryan received his B.S. from the University of San Diego and worked developing next generation sequencing platforms at Complete Genomics prior to joining the University of Pennsylvania CAMB program.
Ryan’s research is focused on studying the role of the transcription-silencing histone variant MacroH2A in regulating stem cell dynamics in the intestinal epithelium during homeostasis, regeneration, and in cancer. There is abundant evidence in the literature that histone variant substitution has direct implications on gene expression and corresponding cell fate, yet this facet of epigenetic control is virtually unstudied in the adult stem cell systems such as the intestinal epithelium.
Outside of lab, Ryan enjoys homebrewing, hiking, badminton, working out, and traveling.
Maryam Yousefi, M.S. - Graduate Assistant
Maryam is a Cell and Molecular Biology Ph.D. student at the University of Pennsylvania. She received my Bachelor and Master in Science in Medical Biotechnology from the University of Tehran in 2009 and 2011. Maryam was recently the recipient of the Howard Hughes International Student Research Fellowship.
Currently, Maryam studies the molecular mechanisms activating quiescent stem cells in the intestinal epithelium following injury. In particular, Maryam applies mouse genetics and molecular biology techniques to better understand the metabolic activation of the quiescent stem cells.
Ning Li, M.D. Postdoctoral Fellow
The intestinal epithelium is organized in a hierarchy of intestinal stem cells (ISCs), with a quiescent of slow-cycling stem cell residing at the top of this hierarchy (marked by Hopx and Bmi1 murine knockin reporter alleles). This quiescent cell, upon activation, gives rise to an actively cycling, Wnthi, Lgr5+ stem cell at crypt base. It is well established that tumor stem cells isolated from colorectal cancers (CRC) exhibit a gene expression profile similar to that of the actively cycling Lgr5+ ISCs. However it remains unclear if tumorigenesis is initiated by uncontrolled proliferation of Lgr5+ ISCs, or if loss of quiescence in the upstream, reserve stem cell compartment is a contributing factor in ontogeny of CRC. Ning’s research is focused on studying the behavior of quiescent ISCs during homeostasis and in tumorigenesis and elucidating the molecular mechanisms driving oncogenic quiescent ISC activation.
Outside of lab, Ning enjoys camping, hiking and photography.
Dong-Hun Woo, Ph.D. - Postdoctoral Fellow
Dong-Hun received his Ph. D. in stem cell biology from the Korea University. During this time, he worked on tissue regeneration through directed differentiation of human pluripotent stem cells into target cell types of the liver, pancreas, and brain. Upon arrival in the US, he initially extended his research into cancer stem cells, studying the molecular mechanisms underlying tumorigenicity of cancer stem cells in glioblastoma at the Lerner Research Institute of Cleveland Clinic in Cleveland, OH.
After joining the Lengner lab, Dong-Hun built on his expertise in stem cell biology human pluripotent cell fate specification by bringing genome editing strategies to bear on induced pluripotent stem (IPS) cell models of human genetic diseases. His current project involves the generation of patient-derived iPS cells, genetic correction of disease-causing mutations, and subsequent specification of the resulting isogenic cell lines into affected intestinal tissue. This model serves as a platform to screen for therapeutic candidates for the treatment of human genetic disorders. Dong-Hun was recently awarded a fellowship from the University of Pennsylvania’s Institute for Regenerative Medicine for his work.
Outside of work, Dong-Hun enjoys driving with his family, collecting souvenirs from cities in the US, and watching baseball games.
Carla Hoge - Vagelos Undergraduate Scholar
Carla is an undergraduate studying in the College of Arts and Sciences at the University of Pennsylvania. She plans to graduate with a degree in Biochemistry and to sub-matriculate in Chemistry. She is a Vagelos Scholar in Molecular Life Sciences.
In the lab, Carla is currently working on using genome editing technology to study the effect of common mutations in in human iPS cell-derived models of colorectal cancer.
Outside of the lab, Carla is in a service fraternity, Alpha Phi Omega, and participates in campus theater- she is the on the iNtuitons Experimental Theatre board.
Former Lab Members:
Kim Davidow (Parada), Research Specialist: Kim is currently a medical student at the Jefferson Medical College of Thomas Jefferson University.
Shan Wang, Visiting Scholar: Shan is currently completing her Ph.D. thesis at the College of Biological Sciences, China Agricultural University in Beijing.
Zhengquan Yu, Postdoctoral Felllow: Zhengquan is currently a Principal Investigator at the State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University in Beijing.