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Molecular and Cellular Biology

Houston, Texas

Image 1: Ovulated mouse cumulus cell oocyte complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.; Image 2: By Yi LI, Ph.D.; Image 3: Mouse oocyte at meiosis I immunostained for tubulin (red) phosphop38MAPK (green) and DNA (blue). By JoAnne Richards, Ph.D.; Image 4: Expanded cumulus cell ooctye ocmplex immunostained for hyaluronan (red), TSG6 (green) and DAN (blue). By JoAnne Richards, Ph.D.; Image 5: Epithelial cells taken from a mouse mammary gland were cultured in a dish and transduced with a retrovirus expressing two genes. The green staining shows green fluorescent protein and the red staining shows progesterone receptor expression. The nucleus of each cell is stained blue. Photomicrograph taken at 200X magnification. By Sandra L. Grimm, Ph.D.; Image 6: Ovarian vasculature (red) is excluded from the granulosa cells (blue) within growing follicles (round structures); Image 7: Ovulated mouse cumulus cell oocyte complex immunostained for matrix proteins hyaluronan and versican. By JoAnne Richards, Ph.D.
Department of Molecular and Cellular Biology
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Michael A. Mancini, Ph.D.

Associate Professor
Department of Molecular and Cellular Biology
Director, Integrated Microscopy Core

Education

Ph.D.: University of Texas Health Science Center, San Antonio
Postdoctoral training: University of Texas Institute of Biotechnology

Research Interest

High Throughput Systems Biology of Gene Regulation
In general terms, a highly dynamic and complex set key regulators underly mechanisms of normal and aberrant gene regulation. Over two decades of reductionist biochemical/molecular studies of gene regulation have identified a great wealth of key factors and interactive pathways, often resulting in important transgenic animal models. Consideration of gene regulator mechanisms at the single cell level, however, have been lacking, largely due to technical hurdles. In the past few years, an increasingly powerful series of automated and quantitive imaging capabilities have come to the fore, providing an altogether new ability of generate and mine a wide series of mechanistic data on gene regulation, with the result being an improving cellular appreciation of how gene regulators function. Further, single cell approaches allow a heretofore impossible view of cellular heterogeneity, as numerous measurements can be made on individual cells that are inherently obscured by population analyses, which is typical in biochemical studies. The results from live or fixed cell studies have led to improved appreciation of the importance of spatiotemporal issues of gene regulators, and a rethinking of how well classically drawn static diagrams may reflect mechanistic cell biology.

Our laboratory has several single cell-based models of nuclear receptor gene regulation in progress, including estrogen and androgen receptors linked to both mechanistic study of wild type and clinical mutations. We have developed live imaging studies focusing upon intracellular dynamics (time lapse, photobleaching), and high throughput system biology level approaches using state of the art automated fluorescence microscopy and image analyses. Multiplexing of numerous quantitative readouts is an intensive effort, including current single cell analyses that capture >500 individual measurements per cell. For example, our current estrogen receptor studies generate quantitative data on NR/CoR trafficking, subnuclear organization, promoter occupancy, large scale chromatin modeling, transcription and the cell cycle---all on a per cell basis---and at 384 well plate speed. The goal of these studies is to general sophisticated molecular, cytological, functional cellular response fingerprints for normal and mutant receptors, and how ligand and RNAi libraries on hand alter these measurements for, ultimately, predictive personalized medicine.

Contact Information

Baylor College of Medicine
One Baylor Plaza, 132CA Cullen Building
Houston, TX 77030

Phone: 713-798-8952
E-mail: mancini@bcm.edu
Lab Web Site:

Selected Publications

  1. Szafran AT, Szwarc M, Marcelli M, Mancini MA. (2008) Androgen Receptor Functional Analyses by High Throughput Imaging: Determination of Ligand, Cell Cycle, and Mutation-Specific Effects. PLoS ONE 3(11): e3605.
  2. Berno V, Amazit L, Hinojos CA, Zhong J, Mancini MG and Mancini MA. (2008). Estrogen receptor-α activated by estradiol or epidermal growth factor induces temporally distinct chromatin remodeling and transcription. PLoS ONE 3:e2286.
  3. Amazit L, Pasini L, AT Szafran, Mielke M, Wu RC, Mancini MG, Hinojos CA, Berno V, O’Malley BW and Mancini MA. (2007). SRC-3/AIB1 function is regulated by phosphocode-directed spatiotemporal dynamics. Mol Cell Biol 27:6913-32. Epub 2007 Jul 23.
  4. Zwart W, Griekspoor A, Berno V, Lakeman K, Jalink K, Mancini MA, Neefjes J and Michalides R. (2007). PKA-induced resistance to tamoxifen is associated with an altered orientation of ERalpha towards co-activator SRC-1. EMBO J 26:3534-44. Epub 2007 Jul 12.
  5. Sharp ZD, Mancini MG, Hinojos CA, Dai F, Berno V, Szafran AT, Smith KP, Lele T, Ingber D and Mancini MA. (2006). Estrogen-receptor-α exchange, and chromatin dynamics are ligand- and domain-dependent. J Cell Science 119:4101-16.
  6. Stenoien DL, Mielke M and Mancini MA. (2002). FRAP reveals that ataxin-1 inclusions contain both fast and slow exchanging components. Nature Cell Biol 4:806-10.
  7. Stenoien DL, Nye A, Mancini MG, Patel K, Dutertre M, O'Malley B, Smith CL, Belmont A and Mancini MA. (2001). Ligand-mediated assembly and real-time cellular dynamics of estrogen receptor-coactivator complexes in living cells. Mol Cell Biol 21:4404-12.
  8. Stenoien DL, Patel K, Mancini MG, Smith CL, O’Malley BW and Mancini MA. (2001). FRAP reveals estrogen receptor-α mobility is ligand- and proteasome-dependent. Nature Cell Biol 2001 3:15-23.
  9. Stenoien DL, Mancini MG, Patel K, Allegretto E, Smith C and Mancini MA. (2000). Subnuclear trafficking of estrogen receptor-α and steroid receptor coactivator-1. Molecular Endocrinology 14:518-34.

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