Faculty Profile

Dr. Meelad M. Dawlaty, Ph.D.

Meelad M. Dawlaty, Ph.D.

Assistant Professor, Department of Genetics

Areas of Research: (1) Epigenetics of embryonic stem cells and development. (2) Epigenetic reprogramming and iPSCs (3) DNA methylation, demethylation and hydroxylation in stem cells, development and cancer. (4) Tet enzymes. (5) Mouse genetics

Professional Interests

Embryonic stem cell biology and development are regulated by epigenetic mechanisms of gene expression involving chromatin modifying enzymes that promote DNA and histone modifications.  We utilize embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mice as model systems to study how these enzymes reshape the epigenome and control gene expression programs to regulate stem cell biology and embryogenesis. The lab specializes in advanced technologies in genome editing and generating complex mouse strains. We integrate genetic, cellular, molecular, biochemical and bioinformatics approaches to dissect epigenetic pathways and mechanisms in stem cells, during development and in diseases.

The Tet family of enzymes (Tet1/2/3) modify the DNA base 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and promote DNA demethylation and gene expression. They are abundant in various cell types including the zygote, ESCs, germ cells, hematopoietic stem cells (HSCs) and neurons. Over the years, our work in the field has defined key functions of Tet enzymes in ESC differentiation, germ cell reprogramming and development (Cell Stem Cell 2011, Developmental Cell 2013, Developmental Cell 2014, Cell Reports 2019) as well as in hematopoietic stem cells (HSCs) and malignancies (Nature Immunology 2015, Cell Reports 2015, Cell Reports 2019), and in memory extinction (Neuron 2013). Recently in my lab:

  • We have shown that the biological roles of Tet enzymes go beyond their enzymatic activity in DNA demethylation. Such non-canonical functions present a novel layer of epigenetic regulation. We study their role in ESC pluripotency and development, as well as in HSCs and hematologic malignancies.
  • We have established that Tet enzymes regulate lineage specification and organogenesis. We research their biologically critical functions in post gastrulation development. 
  • We have found that the DNA binding proteins, Rinf and Idax, partner with Tet enzymes and pluripotency factors in ESCs. We study how they target Tet enzymes and pluripotency factors to gene regulatory regions and control transcription in ESCs and during differentiation.
  • We explore the base 5hmC and its derivatives as independent epigenetic marks. We study their involvement  in regulation of gene expression during development and in onset of diseases.

Our research investigates novel biological roles of DNA modifying enzymes in regulation of stem cell biology, development and cancer. This line of research will unveil new mechanisms of epigenetic regulation by Tets/5hmC, and can lead to identification of unique markers and targets in stem cell applications and for treatment of diseases.

For more details on our research please visit our lab website: https://www.dawlatylaboratory.com

 

Selected Publications

Selected Publications:

  1. Ravichandran M*, Lei R*(co-first author), Tang Q, Zhao Y, Lee J, Ma L, Chrysanthou S, Lorton B, Cvekl A, Shechter D, Zheng D, and Dawlaty M.M., Rinf regulates pluripotency network genes and Tet enzymes in embryonic stem cells, Cell Reports, August (2019)
  2. Ito Ky*, Lee J*, (co-first author), Chrysanthou S, Zhao Y, Josephs K, Sato H, Teruya-Feldstein J, Zheng D, Dawlaty M.M.** (co-corresponding author),Ito K**, Non-catalytic roles of Tet2 are essential to regulate hematopoietic stem and progenitor cell homeostasis, Cell Reports, September (2019)
  3. Dawlaty M.M., Breiling A., Le T., Barrasa I.M., Raddatz G., Gao Q., Powell B.E., Cheng A.W., Faull K.F., Lyko F., and Jaenisch R., Loss of Tet enzymes compromises proper differentiation of embryonic stem cells, Developmental Cell, April (2014)
  4. Dawlaty M.M., Breiling A., Le T., Raddatz G., Barrasa I.M., Cheng A.W.,Gao Q., Powell B.E., Le Z.,  Xu M., Faull K.F., Lyko F., and Jaenisch R., Combined deficiency of Tet1 and Tet2 causes epigenetic abnormalities but is compatible with postnatal development, Developmental Cell, 24(3): 310–23 February (2013) 
  5. Dawlaty M.M., Ganz K, Powell BE, Hu YC, Markoulaki S, Cheng AQ, Gao Q, Kim J, Choi SW, Page DC, and Jaenisch R. Tet1 is dispensable for maintaining pluripotency and its loss is compatible with embryonic and postnatal development. Cell Stem Cell, 9, 166-5, August (2011).
  6. Cimmino L.*, Dawlaty M.M.* (co-first author), Ndiaye-Lobry D., Yap Y. S., Bakogianni S., Yu Y., Bhattacharyya S., Shaknovich R., Geng H., Oricchio E., Lobry C., Mullenders J., King B., Trimarchi T., Aranda-Orgilles B., Liu C., Shen S., Wendel G., Verma A.K., Jaenisch R.**, and Aifantos I. **,Tet1 is a tumor suppressor of hematopoietic malignancy, in press Nature Immunology (2015)

Additional Publications:

  1. Bhattacharyya S., Pradhan K., Campbell N., Mazdo J., Vasantkumar A., Maqbool S., Bhagat T., Gupta G., Suzuki M., Yu Y., Greally J., Steidl U., Bradner J., Dawlaty M.M., Godley L., Maitra A., Verma A. Altered Hydroxymethylation is seen at regulatory regions in pancreatic cancer and regulates oncogenic pathways, Genome Research, 2017 November 27, PMID: 28986391
  2. Feng J, Pena C, Purushothaman I, Engmann O, Waker D, Issler O, Brown A, Doyle M, Harrigan E, Mouzon E, Vialou V, Shen L,Dawlaty M.M., Jaenisch R, Nestler E, Role of Tet1 in regulation of gene expression in nucleus accumbens, Neuropsychopharmacology, 2017 January 25, PMID: 28074830
  3. Yang J, Guo R, Wang H, Ye X, Zhou Z, Dan J, Wang H, Gong P, Deng W, Yin Y, Mao S, Wang L, Ding J, Li J, Keefe DL, Dawlaty M.M., Wang J, Xu G, Liu L., Tet Enzymes Regulate Telomere Maintenance and Chromosomal Stability of Mouse ESCs., Cell Reports. 2016 May 24;15(8):1809-21. PMID: 27184841
  4. Zhao Z. *, Chen L.*, Dawlaty M.M.* (co-first author), Pan F., Li Z., Zhou Y., Cao Z., Shi H., Wang J., Lin L., Chen S., Weeks O., Yuan W., Qin Z, Ni H., Yang FC., Jaenisch R.**, Jin P**, Xu M**., Combined loss of Tet1 and Tet2 promotes B-cell, but not myeloid malignancies in mice, Cell Reports (2015) PMID: 26586431 PMCID: PMC4764044
  5. Wiehle L., Raddatz G, Musch T., Dawlaty M.M., Jaenisch R.J., Lyko F., and Breiling A., Tet1 and Tet2 protect DNA methylation canyons against hypermethylation, Mol. Cell. Biol. (2015)
  6. Theunissen T.W., Powell B.E., Wang H., Mitalipova M., Faddah D., Reddy R., Fan Z.P., Maetzel D., Ganz K., Shi L., Lungjangwa T., Imsoonthornruksa S.,Stelzer Y., Rangarajan S., D’Alessio A, Zhang J., Gao Q., Dawlaty M.M., Young R.A., Gray N.S. and Jaenisch R., Systematic Identification of Culture Conditions for Induction and Maintenance of Naive Human Pluripotency, Cell Stem Cell 15, 1–17, October (2014)
  7. Rudenko A.*, Dawlaty M.M.* (co-first author), Seo J., Cheng A.W., Meng J., Le T, Faull K.F., Jaenisch R**, and Tsai L-H **,Tet1 is critical for neuronal activity-regulated gene expression and memory extinction, Neuron, 6 (79) 1109-1122, September (2013)
  8. Haoyi Wang H.*, Yang H.*, Shivalila C.S.*, Dawlaty M.M., Cheng A.W., Zhang F., and Jaenisch R., One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome Engineering, Cell,9;153(4):910-8, May (2013)
  9.  Piccolo F.M., Bagci H., Brown K., Landeira D., Soza‐Ried J., Feytout A., Moojman D., Hajkova P., Leitch H.G., Tada T., Kriaucionis S, Dawlaty M.M., Jaenisch R., Merkenschlager M. & Fisher A.G., Different roles for Tet1 and Tet2 proteins in reprogramming-mediated erasure of imprints induced by EG cell fusion, Molecular Cell 49(6):1023-33, March (2013)
  10. Huang H., Jiang X., Li Z., Li Y., Song X., He C., Sun M., Chen P., Gurbuxani S., Wang J., Hong G., Elkahloun A., Arnovitz S., Wang J., Szulwach K., Lin L., Street C., Wunderlich M., Dawlaty M.M., Neilly M., Jaenisch R., Yang F., Mulloy J., Jin P., Liu P., Rowley J., Xu M., He C., and Chen J., TET1 plays an essential oncogenic role in MLL-rearranged leukemia, PNAS, USA, 110(29):11994-9 July (2013)
  11. Kim JP, Su SC, Wang H, Cheng AW, Cassady JP, Lodato MA, Lengner CJ, Chung C-Y, Dawlaty M.M., Tsai L-H & Jaenisch R.  Functional integration of dopaminergic neurons directly converted from mouse fibroblasts,  Cell Stem Cell,9(5) 413-419, (2011).
  12. Kim JP, Lengner CJ, Kirak O, Hanna J, Cassady JP, Lodato MA, Wu S, Faddah DA, Steine EJ, Gao Q, Fu D, Dawlaty M.M. & Jaenisch R.  Reprogramming of postnatal neurons into induced pluripotent stem cells by defined factors.  Stem Cells 29, 992-1000 (2011).
  13. Staerk, J., Dawlaty, M.M., Gao, Q., Maetzel, D., Hanna, J., Sommer, C.A., Mostoslavsky, G., & Jaenisch, R.  Reprogramming of human peripheral blood cells to induced pluripotent stem cells. Cell Stem Cell, 7, 20-24 (2010).
  14. Baker, D.J.*,  Dawlaty M.M.*(co-first author), Wijshake, T., Jeganathan, K. B., Malureanu, L., van Ree, J. H., Crespo-Diaz, R., S. Reyes, L. Seaburg, V. Shapiro, A. Behfar, A. Terzic, B. van de Sluis, and J.M. van Deursen. Increased expression of BubR1 protects against aneuploidy and cancer and extends healthy lifespan. Nature Cell Biology, 14(1), 1–9, (2012).
  15. Dawlaty, M. M., Malureanu, L., Jeganathan, K. B., Kao, E., Sustmann, C., Tahk, S.,  Shuai, K., Grosschedl, R., and van Deursen, J. M., Resolution of sister centromeres requires RanBP2-mediated SUMOylation of Topoisomerase IIa. Cell 133, 103-115.  (2008).
  16. Baker, D. J., Dawlaty, M. M., Galardy, P., and van Deursen J. M. , Mitotic regulation of the anaphase promoting complex (APC/C), J. M. Cell Mol Life Sci 64, 589-600 (2007).
  17. Dawlaty, M. M. & van Deursen, J. M. Gene targeting methods for studying nuclear transport factors in mice. Methods 39, 370-8 (2006).

Research Images

Research Image 1 Research Image 2

Click image to enlarge

More Information About Dr. Meelad Dawlaty

Dawlaty Laboratory Website

Link to Publications on PubMed

Material in this section is provided by individual faculty members who are solely responsible for its accuracy and content.

Albert Einstein College of Medicine
Michael F. Price Center
1301 Morris Park Avenue , Room 419
Bronx, NY 10461

Tel: 718.678.1224
Fax: 718.678.1016

Research Information