Pei Wang, Ph.D.Assistant Professor
Baylor College of Medicine, 2004
Dr. Pei Wang received her Ph.D from Baylor College of Medicine where she studied the developmental functions of Alzheimer's disease genes. Then she joined Dr. Seung Kim's laboratory at Stanford University School of Medicine and Howard Hughes Medical Institute for her postdoctoral training where she focused on genetic manipulation of human embryonic stem cells to study endoderm development. Dr. Wang joined the Department of Cellular and Structural Biology in September of 2012; she received a Texas Rising STAR award and a first time tenure track faculty award from the Cancer Prevention and Research Institute of Texas (CPRIT).
Pancreatic ductal adenocarcinoma (PDAC) is a solid tumor characterized by aggressive local invasion, early metastasis, and resistance to conventional chemotherapy or radiation. Further complicating the study of PDAC is the inaccessibility of the pancreas - pancreatic biopsy is extremely rare and risky, so little is known about precursor lesions. Thus, recapitulating the pathogenesis of PDAC in vitro will allow us to develop effective methods to detect early molecular changes for diagnosis and to generate a platform for drug discovery. The immediate goals for are:
- to understand the basis for tumor heterogeneity,
- to establish methods for drug screening using genetically engineered human ductal cells,
- to identify tumor initiating cells (TICs), and
- to characterize the molecular properties of TICs.
The other interest of my lab is to generate insulin producing cells and liver cells from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSC) for modeling disease and for cell replacement therapies. We would establish a step wise differentiation protocol for hESCs and iPSCs. During the differentiation of hESCs into insulin producing beta-cells or liver cells, many intermediate cell stages exist. Therefore, the faithful production and purification of each intermediate cell type permits a more thorough assessment of cell identity and quality. We will use homologous recombination to genetically-modify human ESCs to:
- define the culture conditions for generating intermediate precursor cells for the differentiation of functional insulin producing cells (IPCs) or liver cells,
- identify cell surface markers specific to each intermediate precursor cell type that could be used to purify these cells to homogeneity,
- use genetic techniques, mRNA transfection, and extracellular signaling to drive multipotent progenitors, including hESCs and iPSCs, toward a beta cell or liver cell fate,
- identify novel transcription factors and signaling pathways involved in pancreas and liver development, and
- generate patient-specific iPSCs to study the function of the transcription factors in human pancreas and liver development and disease mechanisms.
Human embryonic stem cell (hESC) and induced pluripotent stem cell (iPSC) culture
Gene targeting in hESC and iPSC
Molecular biology technique
Mouse ES cell targeting and growth
Histologic assessment and disease pathogenesis
Wang P, McKnight KD, Wong DJ, Rodriguez RT, Sugiyama T, Gu X, Ghodasara A, Qu K, Chang HY, Kim SK. (2012) A molecular signature for purified definitive endoderm guides differentiation and isolation of endoderm from mouse and human embryonic stem cells. Stem Cells Dev. 2012 Aug 10;21(12):2273-87.
Hung T, Wang Y, Lin MF, Koegel AK, Kotake Y, Grant GD, Horlings HM, Shah N, Umbricht C, Wang P, Wang Y, Kong B, Langerød A, Børresen-Dale AL, Kim SK, van de Vijver M, Sukumar S, Whitfield ML, Kellis M, Xiong Y, Wong DJ, Chang HY. (2011) Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet. 2011 Jun 5;43(7):621-9.
Wang P, Rodriguez RT, Wang J, Ghodasara A, Kim SK. (2011) Targeting SOX17 in human embryonic stem cells creates unique strategies for isolating and analyzing developing endoderm. Cell Stem Cell. 2011 Mar 4;8(3):335-46.
Wang P, Yang G, Mosier DR, Chang P, Zaidi T, Gong YD, Zhao NM, Dominguez B, Lee KF, Gan WB, Zheng H. (2005) Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. J Neurosci. 2005 Feb 2;25(5):1219-25.
Wang P, Pereira FA, Beasley D, Zheng H. (2003) Presenilins are required for the formation of comma- and S-shaped bodies during nephrogenesis. Development. 2003 Oct;130(20):5019-29.