Xinghua Victor Pan M.D., Ph.D.

Research Scientist in Genetics

Biographical Info

Xinghua (Victor) PAN, Ph.D., M.D.

xinghua.pan@yale.edu

xinghua.pan@gmail.com

Research Scientist, Department of Genetics, Yale University;

Member, Program in Neurodevelopment and Regeneration, Yale University;

Member, NIH program PsychENCODE, Yale University

Biography:

Dr. Xinghua (Victor) Pan earned his Ph.D. degree with Drs. CC Tan and Z Geng from the Institute of Genetics, Fudan University School of Life Science, Shanghai in China. His thesis research was on the genetic associations between HLA and autoimmune diseases SLE and Myasthenia Gravis. He obtained his M.D. degree (equivalent) from the Southern Medical University (previously called First Military Medical University), Guangzhou, China. After these, he got his postdoctoral training at the National Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC) with Dr. Min WU, identifying a candidate tumor suppressor gene, and got a support from the China Postdoctoral Science Foundation. Beginning in December 1994, he served as Associate Professor in Genetics in the Department of Biology /Medical Genetics, Second Military Medical University, Shanghai, China, where he obtained a grant from the National Natural Science Foundation of China (NSFC), with which he established nm23 transgenic mouse and elucidated its effect on hepatocarcinoma. In addition, he studied EBV BHRF1 on nasopharyngeal carcinoma, reconstructed the phylogenetic tree for MHC genes. In 1997, Dr. Pan as a Postdoctoral Fellow joined Dr. Sherman Weissman’s laboratory in the Department of Genetics, Yale University School of Medicine, and developed an approach (GADAV) for unconditionally globally scanning of DNA mutations. From 2000 to 2004, he worked with Dr. Roger Lasken for Molecular Staging Inc. as a Research Scientist in Genomics Section and then Enzymology Leader, conducted the product development (REPLIg) based on MDA for whole-genome-amplification, which is currently used world-wide and regarded as one of the best WGA technologies.

Dr. Pan joined Yale School of Medicine as Associate Research Scientist in Dr. Weissman’s laboratory in 2004, promoted to Research Scientist in 2014, directing a group on functional genomics for single cells. His researches were/are supported by grants from NIH (P01, P30, P50, R01, R30, R21 in genomics, stem cell, cancer, and neuroscience), Connecticut stem cell committee and other foundations. Dr. Pan has > 50 peer-reviewed papers and > 20 reviews published, 6 patents issued and 3 patents in pending. He is an Invited Reviewer or Editor for multiple international journals and foundations, a Committee Member for several academic conferences, and an Invited/Featured Speaker and Section Chair in several academic meetings.

Education & Training

M.D. Southern Medical University (with its previous name as the First Military Medical University) (1985)

Ph.D. Fudan University (1993)

Postdoc. Assoc Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), (1993-1994)

Postdoc Fellow Yale University School of Medicine, Genetics (1997-1999)

Research Interests

Single Cell Functional Genomics: My group focuses on the development and application of cutting edge technologies for genome-wide analysis of single cells and low numbers of cells for the functional genomic elements, in aspects of genomics, epigenomics and transcriptomics, with the support of Dr. Sherman Weissman. We began with whole genome amplification technology, WPA (PNAS 2008), which was invented on the basis of my experience in development of REPLIg kit (at Molecular Staging Inc. with Dr. Roger Lasken), and was then adapted for full length and whole transcriptome amplification and expression profiling (RNA-seq) (PNAS 2013a). Combining these together, we established the proof of principle for co-detection and sequencing of gDNA and mRNA from the same single cells (Scientific Reports, 2014). We have in addition developed a simple and robust method for telomere length measurement of single cells (PNAS 2013b). We have also independently renovated RRBS for single cell analysis, and extended the genome-wide bisulfite sequencing to the single cell level. Recently we have been building up on a different method for genome-wide CpG methylation pattern sequencing independent of bisulfite conversion, which are particularly suitable for single cell analysis, and we again approach a new method for detection of condensed chromatin regions for single cells (manuscripts in submission or preparation). We adapt these technologies into other advanced systems and platforms especially high throughput sequencing (NGS) and microfluidics such as Fluidigm platform and collaborate with other investigators to study the gene regulation network for induced pluripotent stem cells (iPSC), embryonic stem cells (ESC), adult stem cells (HSC, hMSC), neurons, cells of the immune system and cancers, and have been starting an effort to apply these technologies into translational medicine.

Manuscripts under Review or Revision

1.#. Yang J, Seay M, Tanaka Y, Euskirchen G, Snyder M, Park I, Pan X*, Weissman SM*. Heterogeneity and cell cycle related changes in single cell transcriptomes of early hematopoietic precursors

2#. Han Lin, Huajun Wu, Haiying Zhu, Markus Riester, Kun-Yong Kim, Sadie Marjani, Ghia Euskirchen, Michael Snyder, In-Hyun Park, Sherman M. Weissman, Franziska Michor*, Rong Fan*, Xinghua Pan*, Single-cell genome-wide CpG methylation patterns based on enzymatic recognition and selective amplification.

3#. Yoshiaki Tanaka, Eriona Hysolli, Juan Su, Yangfei Xiang, Kun-Yong Kim, Yumei Li, Mei Zhong, Ghia Euskirchen, Michael Snyder, Sherman Morton Weissman, Xinghua Pan, and In-Hyun Park. Transcriptome landscape dynamics in human somatic cell reprogramming.

Recent Publications

2014:

1. Han L, Zi X, Garmire LX, Wu Y, Weissman SM, Pan X, Fan R. (2014) Co-detection and sequencing of genes and transcripts from the same single cells enabled by a microfluidics platform. Scientific Reports, 2014 Sep 26;4:6485. doi: 10.1038/srep06485. PMID: 25255798 (a corresponding author).

2. Zuo L, Lu L, Tan Y, Pan X, Cai Y, Wang X, Hong J, Zhong C, Wang F, Zhang XY, Vanderlinden LA, Tabakoff B, Luo X. (2014) Genome-Wide Association Discoveries of Alcohol Dependence. American Journal on Addictions, 23: 526–539. PMID: 25278008.

3. Zuo L, Wang K, Wang G, Pan X, Zhang X, Zhang H, Luo X (2014). Common PTP4A1-PHF3-EYS variants are specific for alcohol dependence. Am J Addict. 23(4):411-4. PMID: 24961364

4. Kim KY, Hysolli E, Tanaka Y, Wang B, Jung YW, Pan X, Weissman SM, and Park IH. (2014) X chromosome of female cells shows dynamic changes in status during human somatic cell reprogramming. Stem Cell Reports, 15;2(6):896-909. PMID: 24936474.

5. Dan J, Liu Y, Liu N, Chiourea M, Okuka M, Wu T, Ye X, Mou C, Wang L, Wang L, Yin Y, Yuan J, Zuo B, Wang F, Li Z, Pan X, Yin Z, Chen L, Keefe DL, Gagos S, Xiao A, Liu L. (2014) Rif1 maintains telomere length homeostasis of ESCs by mediating heterochromatin silencing. Dev Cell, 29(1):7-19. PMID: 24735877

6. Guo S, Zi X, Schultz V, Cheng J, Zhong M, Koochaki S, Megyola CM, Pan X, Heydari K, Weissman SM, Gallagher PG, Krause DS, Fan R, Lu J. (2014) Non-stochastic reprogramming from a privileged somatic cell state. Cell, 156(4):649-62. PMID: 24486105.

2013:

7. Tanaka Y, Kim KY, Zhong M, Pan X, Weissman SM, and Park I-H. (2013) Transcriptome regulation in pluripotent stem cells by methyl CpG-binding protein 2 (MeCP2). Human Molecular Genetics, 23(4): 1045-55. PMID: 24129406

8. Wang Y, Yang F, Zhang HX, Zi XY, Pan XH, Chen F, Luo WD, Li JX, Zhu HY, Hu YP. (2013) Cuprous oxide nanoparticles inhibit the growth and metastasis of melanoma by targeting mitochondria. Cell Death and Disease 4,e783; doi:10.1038/cddis.2013.314.

9. Wang F, Pan X, Kalmbach K, Seth-Smith ML, Ye X, Antumes DM, Yin Y, Liu L, Keefe DL, Weissman SM. (2013) Robust measurement of telomere length in single cells. Proc Natl Acad Sci U S A. 110 (21): E1906–E1912. PMID: 23661059 (a corresponding author). It is shown in PNAS comments: New ruler for telomere length, May 10, 2013 by Sarah CP Williams; highlighted in “This week in PNAS - In this Issue”: May 21, 2013 by C.R.; and featured as “Telomere length measurement in single cells” by Hannah Stower published in Nature Reviews Genetics, 14, 444, (2013), doi:10.1038/nrg3529, June 18, 2013.

10. Zhang Y, Schulz V, Reed B, Wang Z, Pan X, Mariani J, Euskirchenc G, Snyder M, Vaccarino FM, Ivanova N, Weissman SM, Szekely AM. (2013). Functional genomic screen of human stem cell differentiation reveals pathways involved in neurodevelopment and neuodeeneration. Proc Natl Acad Sci U S A. 110(30): 12361-6. PMID: 23836664.

11. Zuo L, Wang K, Zhang X, Pan X, Wang G, Krystal JK, Zhang H, Luo X. (2013). Sex chromosome-wide association analysis suggested male-specific risk genes for alcohol dependence. Psychiatric Genetics. 23(6):233-8. PMID: 23907288.

12. Zuo L, Wang K, Zhang X-Y, Pan X, Wang G, Tan Y, Zhong C, Krystal JH, State M, Zhang H, Luo X. (2013). Association between common alcohol dehydrogenase gene (ADH) variants and schizophrenia and autism. Human Genetics, 132(7):735-43. PMID: 23468174.

13. Pan X, Durrett RE, Zhu H, Tanaka Y, Li Y, Zi X, Marjani SL, Euskirchen G, Ma C, Lamotte RH, Park IH, Snyder MP, Mason CE, Weissman SM. (2013). Two methods for full-length RNA sequencing for low quantities of cells and single cells. Proc Natl Acad Sci U S A. 110(2):594-9. PMID: 23267071(a corresponding author).

Selected early publications:

14. Qu L, Li Y, Pan X, Zhang P, LaMotte RH and Ma C. (2012). Transient receptor potential canonical 3 (TRPC3) is required for IgG immune complex-induced excitation of dorsal root ganglion neurons. The Journal of Neuroscience. 32(28):9554-62. PMID: 22787041.

15. Wang F, Yin Y, Ye Xiaoying, Liu K, Zhu H, Wang L, Chiourea M, Okuka M, Jia G, Dan, J, Zuo B, Li M, Zhang Q, Liu N, Chen L, Pan X, Gagos S, Keefee D, and Lin L. (2012). Molecular insights into the heterogeneity of telomere reprogramming in induced pluripotent stem cells (iPSCs). Cell Research. 22:757–768, PMID: 22184006.

16. Liu Z, Hu Z, Pan X, Li M, Togun TA, Tuck D, Pelizzola M, Huang J, Ye X, Yin Y, Liu M, Li C, Chen Z, Wang F, Zhou L, Chen L, Keefe DL, Liu L. (2011). Germline competency of parthenogenetic embryonic stem cells from immature oocytes of adult mouse ovary. Hum Mol Genet. 20(7):1339-52. PMID:21239471.

17. Yasukochia Y, Maruyamab O, Mahajana MC, Paddenc C, Euskirchend GM, Schulze V, Hirakawaf H, Kuharag S, Pan XH, Newburgerc PE, Snyder M, Weissmana SM. (2010). X chromosome-wide analyses of genomic DNA methylation states and gene expression in male and female neutrophils. Proc Natl Acad Sci U S A. 107(8): 3704-3709. PMID: 20133578.

18. Pan X, Urban AE, Dean P, Vincent S, Grubbert F, Hu Y, Snyder M, Weissman SM. (2008) A procedure for highly specific, hypersensitive and unbiased whole genome amplification. Proc Natl Acad Sci U S A. 105(40):15499-504. PMID: 18832167 (a corresponding author).

19. Pan X, Weissman SM. (2002) An approach for global scanning of single nucleotide variations. Proc Natl Acad Sci U S A. 99(14):9346-51. PMID: 12093903.

Recent Reviews/book chapter:

2011-2014

1. Pan X. (2014). Single Cell Analysis: From Technology to Biology and Medicine. Single-Cell Biology 3(1). pii: 106. http://dx.doi.org/10.4172/2168-9431.1000106. PMID:25177539 (the corresponding author).

2. Liu N, Liu L, Pan X. (2014) Single-cell analysis of the transcriptome and its application in the characterization of stem cells and early embryos. Cell Mol Life Sci. (14):2707-15. PMID: 24652479 (a corresponding author).

3. Zhao Z, Pan X, Liu L, Liu N. (2013) Telomere length maintenance, shortening, and lengthening. J Cell Physiol. 229(10):1323-9. PMID: 24374808

4. Pan X, Urban AE and Weissman S. (2013) Chapter 20: Enriching DNA sequencing with nucleotide variation by thymidine glycosylase combined with suppression PCR. In: PCR Technology: Current Innovations (3rd Edition), edited by Tania Nolan and Stephen A. Bustin, CRC Press. pp. 285-297.

5. Xu Z, Xie J, Meng J, Li P, Pan X, Zhou Q. (2013) Non-invasive prenatal diagnosis: a comparison of cell free fetal DNA (cffDNA) based screening and fetal nucleated red blood cell (fnRBC) initiated testing. North America Journal Medicine and Science, 6(4): 199-204. DOI: 10.7156/najms.2013.0604199.

6. Grommisch, B, DiAdamo AJ, Pan X, Ma D, Xu Z, Xie J, Qi Y, Li P. (2013) Biobanking of residual specimens from diagnostic genetic laboratories: standard operating procedures, ethical and legal considerations, and research applications. North America Journal Medicine and Science, 6(4): 205-212. DOI: 10.7156/najms.2013.0604205.

7. Pan XH, Zhu HY, Marjani SL. (2011). Technological advances in single-cell genomic analyses. Hereditas (appeared in Pubmed as YiChuan) , 33(1): 17-24. PMID: 21377954 (the corresponding author).


Education & Training

M.D.
First Military Medical University (1985)
Ph.D.
Fudan University (1993)
Postdoctoral Associate
Cancer Institute, CAMS & PUMC, Beijing, China, National Kay Lab on Molecular Oncology (1993 - 1994)
Postdoctoral Fellow
Yale University School of Medicine, Genetics (1997 - 1999)

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