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M. Michele Pisano, Ph.D.

PisanoM. Michele Pisano, Ph.D.
Professor, Department of Molecular, Cellular & Craniofacial Biology
Professor, Department of Pharmacology & Toxicology
Research Director, Laboratory of Molecular Craniofacial Development
University Scholar

I. Overview:  Molecular, Genetic and Epigenetic Developmental Mechanisms

Birth defects and congenital developmental disabilities constitute an underappreciated global pandemic. Eight million infants are born with birth defects each year ¬– nearly forty percent of these infants and children die before the age of 5. Despite unprecedented strides in medicine and healthcare, birth defects remain the leading worldwide cause of infant mortality and childhood morbidity.  These statistics notwithstanding, public health efforts in the United States and globally have failed to categorize the prevention and treatment of birth defects as national health priorities. Even international agencies such as the World Health Organization and the United Nations have failed to evolve an appreciation for the magnitude of the human health crisis associated with birth defects and developmental disabilities. In June of 2006, the United Nations General Assembly adopted a declaration urging the nations of the world to strengthen their battle against AIDS – a  disease termed by then UN Secretary-General Kofi Annan as the “greatest challenge of our generation”.  Indeed, 3 million adults and children die from AIDS annually – a Fluorescent cells copy.jpgsobering statistic, but one that is exceeded by the 3.3 million infants and children that die annually from birth defects and congenital developmental disabilities. Even in the United States, a country with one of the most advanced healthcare systems in the world, a child is born with a birth defect and two babies with low birthweight – every three minutes. Moreover, despite unprecedented intellectual and technological strides in the biomedical sciences, including sequencing of the human genome and advances in prenatal care/diagnostics – the overall incidence of birth defects and developmental disabilities is not declining and the underlying causes of nearly 70 percent of all birth defects remain unknown.  In view of this, the research activities in our laboratory seek to provide a better understanding of the molecular, genetic, and epigenetic basis of normal development, as well as elucidate the genes and molecules that when altered result in the genesis of birth defects and infant low birthweight.  Particular focus is centered on prenatal, maternal and child health issues relevant to the state of Kentucky. A combination of unique characteristics in the state, including socio-economic factors and an unusually high percentage of women who continue to smoke and drink during their pregnancy, contribute to an increased prevalence of major birth defects such as oro/facial clefting, neural tube defects, fetal alcohol- and maternal diabetes-induced embryopathies, as well as infant low birthweight and developmental disabilities.

Hat Map copy.pngII. FUNDED GRANTS

P.I.:    M. Michele Pisano
P.I.   Rachel Neal
Title:     “Developmental Cigarette Smoke Exposure: Biomarkers of Neurotoxicity”
Funding Agency:  NIH R21DA027466
Total Direct Costs Funded:  $400,000
Project Period:      2009 - 2012

P.I.:    M. Michele Pisano
P.I.   Thomas B. Knudsen
Title:       “Response Signatures of Alcohol Related Birth Defects”
Funding Agency:  NIH R01 AA13205
Total Direct Costs Funded:  $221,582.

P.I.:    M. Michele Pisano
P.I.:  Thomas B. Knudsen
Title:       “Perinatal Programming of Breast Cancer:  Fat and Estrogens”
Funding Agency:  NIH R01 ES013821
Total Direct Costs Funded:  $104,000.
Subproject Director:    M. Michele Pisano
P.I.:  Robert M Greene
Title:       “Molecular Determinants of Developmental Defects”
Subroject:  “Pre- and Postnatal Tobacco Smoke Exposure:  Effects on Neurocognitive Development”
Funding Agency:  NIH P20 RR/DE017702
Subproject Direct Costs Funded: $540,000

Montage 1 PIsano.jpgP.I.:    M. Michele Pisano
Title:     “Developmental Neurotoxicity of Prenatal Environmental Tobacco Smoke Exposure”
Funding Agency: University of Louisville Center for Environmental Genomics and
Integrative Biology,  Kenneth Ramos, Director.
Direct Costs Funded: $30,000.       
Co-I.:    M. Michele Pisano
P.I.:    Robert M. Greene
Title:       “Nutritional Epigenetics and Orofacial Development”
Funding Agency:  NIH R01 DE018215
Total Direct Costs Funded:  $900,000.

Co-I.:    M. Michele Pisano
P.I.:    Robert M. Greene
Title:       “Transcriptional Coactivators and Pregnancy Outcomes”
Funding Agency:  NIH R01 HD053509
Total Direct Costs Funded:  $1,321,365.

Pisano Schematic copy.jpgIII. PUBLICATIONS

  • Mukhopadhyay P., F. Rezzoug,  C.L. Webb, M.M. Pisano, R.M. Greene.  Suppression of chondrogenesis by Id helix-loop-helix proteins  in embryonic  orofacial tissue. Differentiation 77:462-472 (2009).
  • Warner D.R., H. Smith,  C.L. Webb, R.M. Greene, M.M. Pisano.  Expression of Wnts in the developing murine  secondary palate.  International  Journal of Developmental Biology 53:1105-1115 (2009).
  • Bhattacherjee  V,  K.H. Horn, S. Singh, C.L. Webb, M.M. Pisano, R.M. Greene.  CBP/p300 and associated transcriptional coactivators exhibit distinct expression patterns during murine craniofacial and neural tube development. International  Journal of Developmental Biology 53:1097-1104 (2009).
  • Singh S., C.L. Webb, R.M. Greene, M.M. Pisano.  Arsenate-induced apoptosis in murine embryonic maxillary mesenchymal cells via mitochondrial-mediated oxidative injury.  Birth Defects Research  - Part. A  88:25-34 (2010).
  • Pisano M.M., V. Bhatacherjee,  L. Wong, A. Henley, R. Finnell, R.M. Greene.  Novel folate binding protein 1 interacting proteins in embryonic orofacial tissue. Life Sciences  86:275-280 (2010).
  • Mukhopadhyay P., K.H. Horn, R.M. Greene, M.M. Pisano.  Prenatal exposure to environmental tobacco  smoke alters gene expression in the developing murine hippocampus. Reproductive Toxicology 29:164-175 (2010).
  • Horn K., D.R. Warner, M.M. Pisano, R. M. Greene.  PRDM1 expression in the developing mouse embryo. Acta Histochemistry. (In Press; published online Oct. 23, 2009; doi:10.1016/j.acthis.2009.09.006) (2010).
  • Mukhopadhyay P., G. Brock, V. Pihur, C. Webb, M.M. Pisano, R.M. Greene. Developmental microRNA expression profiling of muring embryonic orofacial tissue. Birth Defects Research - Part A  88:511-534 (2010).
  • Greene R.M., M.M. Pisano.  Palate Morphogenesis:  Current Understanding and Future Directions.  Birth Defects Research - Part C 90:133-154 (2010).
  • Lu W., Guzman A., Yang W., Chapa-Garcia C.J., Shaw G.M., Greene R.M., Pisano MM, Lammer EJ, Finnell RH  Zhu H.  Are genes encoding  critical transcriptional activators for murine neural tube development associated with human spina bifida?  BMC Medical Genetics 11:141-xxx (2010).
  • Warner D, P. Mukhopadhyay, P, G. Brock,  V.  Pihur,  M.M. Pisano, R.M.Greene.  TGFß and Wnt-3a interact to induce unique gene expression profiles in murine embryonic palate mesenchyme cells.  Reproductive Toxicology , in press (2010).   

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