Lemischka and Moore Labs - Research

Welcome to the
Lemischka and Moore Laboratories
for Integrative Stem Cell Biology

Ihor Lemischka

   The focus of our research is to understand the molecular and cellular nature of the undifferentiated stem cell "states", and how such states are altered during a change in cell fate. The underlying rationale for our studies is that the complement of gene-products and their inter-relationships that exist in stem cells accounts for their remarkable abilities to balance self-renewal and differentiation decision processes. We study both adult and embryonic stem (ES) cells, primarily from the mouse, but also from the human. As a first step, we have comprehensively identified most, if not all gene-products that are expressed in highly purified hematopoietic stem cell (HSC). We performed similar analyses in mouse ES cells. Such molecular "signatures" provide parts-lists that are available to the stem cells. The challenge has been to functionally address the roles that these molecules play in mediating the biological properties of HSC and ES cells. Further, we would like to understand how these molecular components are "wired" into regulatory signaling and transcriptional networks.

   To explore these issues we have utilized a number of global gene-expression perturbation technologies, such as inhibitory short hairpin RNA (shRNA). We have successfully down regulated the expression levels of candidate regulatory molecules in both HSC and ES cells. A number of these play crucial regulatory roles in processes such as self-renewal, proliferation, and differentiation. We have further developed strategies that allow the analyses of cell-fate change dynamics at multiple biochemical and molecular levels in response to defined and precisely controlled changes in the expression levels of key regulatory molecules. These strategies have provided the first in-depth view of how a cell-fate decision actually occurs at the transcriptional, post-transcriptional, translational, and post-translational levels. An important aspect of our overall efforts is computational and quantitative analyses. We anticipate that our approach will yield a systems biology level description and understanding of stem cell decision processes. This in turn, will have profound implications in future efforts focused on applying basic stem cell research in translational as well as clinical contexts.

Kateri Moore

      My research is focused on defining the cellular and molecular nature of hematopoietic stem cells (HSCs) and the molecular cross-talk that occurs between stem cells and their niche. We use transgenic mouse models to study HSC during normal homeostasis and after stress. We are interested in the basic property of self-renewal and whether HSCs really do self-renew to full functional potential when they undergo cell division. The lab is also using specific factors to directly induce hemogenesis from somatic cells, both mouse and human. We have shown that the induction process recapitulates developmental hematopoies and molecular cues from these studies have led to a new investigation of HSC precursor populations during embryonic development. Overall our studies will have broad implications on the behavior of all stem cells including those that contribute to metastatic cancer and leukemias. 

Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells. Pereria et al.

lab info

Ihor Lemischka

212-659-8228 (office)
212-659-8283 (lab)
212-803-6740 (fax)

Kateri Moore

212-659-8312 (office)
212-659-8283 (lab)
212-803-6740 (fax)

lab members:
graduate student:
Bernitz, Jeffrey
Daniel, Michael
Katz, Suzanna
Kim, Huen Suk
Lau, Kwun Kit
Yuan, Ye (James)

stem cell core:
D'Souza, Sunita
Alexeeva, Vera
Ayudin, Iraz

see photos and more here.
key publications

Bernitz JM, Kim HS, MacArthur B, Sieburg H, Moore K.,
Hematopoietic Stem Cells Count and Remember Self-Renewal Divisions.
Cell. 2016 Nov 17;167(5):1296-1309.e10. doi: 10.1016/j.cell.2016.10.022. PubMed PMID: 27839867.
Commented in Dev Cell. 2016 Nov 21;39(4):390-391. doi: 10.1016/j.devcel.2016.11.005.
Fast EM1, Ira Zon L2.
Aging Hematopoietic Stem Cells Make Their History.

Pereira CF, Chang B, Gomes A, Bernitz J, Papatsenko D, Niu X, Swiers G, Azzoni E, de Bruijn MF, Schaniel C, Lemischka IR, Moore KA.,
Hematopoietic Reprogramming In Vitro Informs In Vivo Identification of Hemogenic Precursors to Definitive Hematopoietic Stem Cells. 
Developmental Cell. ; 36(5):525-39,
Developmental Cell Previews:
Tracking HSC Origin: From Bench to Placenta, V. Calvanese and H.K.A. Mikkola, Dev Cell, 

Brosh R, Hrynyk I, Shen J, Waghray A, Zheng N, Lemischka IR.,
A dual molecular analogue tuner for dissecting protein function in mammalian cells. 
Nat Commun. 2016 May 27;7:11742. doi: 10.1038/ncomms11742. 
PubMed PMID: 27230261
Central PMCID: PMC4895048.

Lee DF, Su J, Kim HS, Chang B, Papatsenko D, Zhao R, Yuan Y, Gingold J, Xia W, Darr H, Mirzayans R, Hung MC, Schaniel C, Lemischka IR.,
Modeling familial cancer with induced pluripotent stem cells.
Cell. 2015 Apr 9;161(2):240-54. doi: 10.1016/j.cell.2015.02.045.
PMID: 25860607 

see more publications here.