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Michal  Zalzman
 

Michal Zalzman Ph.D.

Academic Title: Assistant Professor
Primary Appointment: Biochemistry and Molecular Biology
Secondary Appointments: Otorhinolaryngology-Head & Neck Surgery
mzalzman@som.umaryland.edu
Location: 108 N Greene Street, 002
Phone: 410-706-7879
Fax: 410-706-7886
Lab: 410-706-7886

Personal History:

Dr. Zalzman is a molecular cell biologist and an established stem-cells expert since the year 2000. She received her B.Sc. degree from the University of Bar Ilan, Israel, and M.Sc. and Ph.D. from Tel Aviv University, Israel, in the department of Human Molecular Genetics and Biochemistry. She then completed post-doctoral work at the National Institute on Aging/NIH, in the developmental Genomics and Aging Section in the Laboratory of Genetics. She holds a worldwide patent from WIPO, and is a full member of the University of Maryland Center for Stem Cell Biology and Regenerative Medicine.

Research Interests:

Fig. 1: Co-localization of markers (green) on human telomeres (red). Dapi stains DNA (blue).

The Zalzman lab studies fundamental mechanisms controlling cellular immortality and telomere repair. We are exploring these topics in two major systems: adult stem cells and cancer cells.

Unlike normal cells in our body, cancer cells don’t age. They activate mechanisms to bypass the aging process, gain immortality and continue to replicate indefinitely. Our goal is to characterize the components of a novel apparatus that allows cancer to bypass cell aging in order to ultimately allow the development of a new class of agents designed to target cancer immortality.

Fig.2: Cancer begins with mutated clones probably when a DNA-checkpoint controlling gene is disabled. However, to appear as a clinically observable tumor a premalignant clone would have to divide 60-80 times. Nevertheless, as a tumor suppressor mechanism, telomeres (in red) at the end of the chromosomes (blue) act like a biological clock, shortening with each cell division. As they shorten they limit cells’ ability to proliferate. Therefore, to facilitate cancerous transformation a cell has to activate telomere extension, overcome this limit and gain immortality.

For our stem cell study, we use adult stem cells as an in vitro model for aging and telomere damage. Currently, the clinical use of adult stem cells is very limited as their potential to replicate and form different tissue types is reduced in aged patients and due to further accelerated aging when expanded in tissue cultures.

Our lab develops novel protocols to enhance the replicative lifespan and the differentiation potential of adult stem cells. This research will allow the large scale expansion of adult stem cells required for future therapies of numerous diseases that are currently candidates for stem cell treatment, such as bone and cartilage reconstructive surgeries, multiple sclerosis, Alzheimer’s, diabetes, and Parkinson’s disease.

Lab Techniques and Equipment:

Laboratory Approaches

The Zalzman lab has extensive experience in isolation of adult human stem cells from multiple tissue sources such as the bone marrow, tonsils, pancreas, liver and adipose (fat) tissue. Our lab specializes in propagation of primary adult stem cell cultures, establishment of stem cell lines, long-term culture, characterization, and tissue engineering of stem cells.

Fig. 3: Generation of Mesenchymal Stem Cells (MSCs) lines in our laboratory.  We currently generate MSCs lines from 3 different adult human tissues (independently): (a). Tonsils, (b). Adipose tissue and (c). Bone marrow. We then differentiate the MSCs to multiple tissues for applications in regenerative medicine: (right to left) smooth muscle cells, osteocytes (bone), chondrocytes (cartilage), Neurons (Nerve cells) and Adipocytes (fat).

Our cancer projects includes multiple techniques such as cancer cell lines establishment, tissue array studies, functional genomics, xenograft models in mice and tumor histological analysis.

For our research we use advanced molecular cell biology and cytogenetic techniques such as: M-FISH, Q-FISH, telomere FISH combined with co-immunostaining, G-band karyotyping and sister chromatid exchange (SCE) assay. Biological assays such as apoptosis and viability assays, cell proliferation assay, telomerase activity (TRAP) assays and cell survival assay. For gene functional analysis we use targeted gene knockout, as well as gene knockdown, gene rescue experiments by exogenous transgene gene induction, inducible gene expression systems (tet inducible system or the CreERT2 system). Additional molecular biology methods: RT-PCR, PCR, qPCR, Microarrays, Western blot, co-immunofluorescence staining for multiple antigens, Flow cytometery analysis and FACS sorting.


Grants & Contracts:

Maryland Stem Cells/TEDCO investigator Initiate Grant


Publications:

Selected Publications

  1. Zalzman M, Gupta S, Giri RK, Berkovich I, Sappal BS, Karnieli O, Zern MA, Fleischer N, Efrat S. Reversal of hyperglycemia in mice by using human expandable insulin-producing cells differentiated from fetal liver progenitor cells. PNAS. 2003. 100(12):7253-8.
  2. Zalzman M, Anker-Kitai L, Efrat S. Differentiation of human liver-derived, insulin-producing cells toward the beta-cell phenotype. Diabetes. 2005. 54(9):2568-75
  3. Ouziel-Yahalom L, Zalzman M, Anker-Kitai L, Knoller S, Glandt M, Herold K and Efrat S. Expansion and re-differentiation of adult human pancreatic islets cells. Biochem Biophys Res Commun. 2006. 341(2):291-8.
  4. Nishiyama A, Xin L, Sharov AA, Thomas M, Mowrer G, Meyers E, Piao Y, Mehta S, Yee S, Nakatake Y, Stagg C, Sharova L, Correa-Cerro LS, Bassey U, Hoang H, Kim E, Tapnio R, Qian Y, Dudekula D, Zalzman M, Li M, Falco G, Yang HT, Lee SL, Monti M, Stanghellini I, Islam MN, Nagaraja R, Goldberg I, Wang W, Longo DL, Schlessinger D, Ko MS. Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors. Cell Stem Cell. 2009. 5(4):420-33.
  5. Zalzman M, Falco G, Sharova LV, Nishiyama A, Thomas M, Lee SL, Stagg CA, Hoang HG, Yang HT, Indig FE, Wersto RP, Ko MS. Zscan4 regulates telomere elongation and genomic stability in ES cells. Nature (article). 2010. 464(7290):858-63.
  6. Ouziel Yahalom l., Cavelti-Weder C., Zalzman M., Keyzer C, Li WC., Guo L., Sharma A., Lei J, Markmann J, Bonner-Weir S., Ductal heterogeneity suggests a subpopulation of ductal cells as postnatal pancreatic progenitors in human and mouse. Endocr Rev. 2011. 32:495.
  7. Nishiyama A, Sharov AA, Piao Y, Amano M, Amano T, Hoang HG, Binder BY, Tapnio R, Bassey U, Malinou JN, Correa-Cerro LS, Yu H, Xin L, Meyers E, Zalzman M, Nakatake Y, Stagg C, Sharova L, Qian Y, Dudekula D, Sheer S, Cadet JS, Hirata T, Yang HT, Goldberg I, Evans MK, Longo DL, Schlessinger D, Ko MS. Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells. Sci Rep. 2013. 3:1390