Jean Fan, Ph.D.

12 Oxford Street, Naito 031, Cambridge, MA 02138
jeanfan@fas.harvard.edu
https://jef.works

(Updated May 16, 2019)


RESEARCH INTERESTS

My research strives to develop a comprehensive understanding of key genetic, epigenetic, and transcriptional programs controlling cellular development, differentiation, and maturation using high-throughput single-cell multi-omics approaches. I am particularly interested in developmental trajectories in the context of pediatric cancers and how disruptions to normal developmental trajectories drive tumor formation and progression to ultimately shape clinical outcomes. I develop new open-source computational software for analyzing single-cell multi-omics data that can be tailored and applied to diverse cancer types and biological systems.


EDUCATION

Postdoctoral Fellow, Department of Chemistry & Chemical Biology (CCB), Harvard University, Cambridge, MA. (2018-Current)
Faculty Mentor: Xiaowei Zhuang, Professor of CCB and of Physics.
Projects: Computational methods for analyzing spatially resolved single-cell transcriptomics data.

Ph.D. in Bioinformatics and Integrative Genomics, Division of Medical Science, Harvard University, Boston MA. (2013-2018)
Faculty Mentor: Peter Kharchenko, Professor of Biomedical Informatics.
Dissertation: Computational and Statistical Methods for Characterizing Single-cell Heterogeneity.

B.Sc. Double major in Biomedical Engineering and Applied Math & Statistics, Whiting School of Engineering, Johns Hopkins University, Baltimore, MD. (2009-2013)


RESEARCH GRANTS

NIH NCI F99/K00. Role: Principal Investigator. Statistical Methods for Characterizing Tumor Heterogeneity at the Single-Cell Level. (2017-Current)

NIH NRSA F31. Role: Principal Investigator. Computational Analysis of Subclonal Evolution in Chronic Lymphocytic Leukemia. (2016-2017)

NSF GRFP. Role: Principal Investigator. A Bayesian Network Approach for Assessing Factors in Complex Disease Etiology. (2013-2016)


PUBLICATIONS

(* Equal contributions)

Selected Peer-reviewed Publications

  1. Fan J*, Lee H*, Lee S, Ryu D, Lee S, Kim SJ, Kim K, Barkas N, Park P, Park WY, Kharchenko PV. Linking transcriptional and genetic tumor heterogeneity through allele analysis of single-cell RNA-seq. Genome Research (2018) doi:10.1101/gr.228080.117
  2. Lake B*, Chen S*, Sos B*, Fan J*, Yung Y, Kaeser GE, Duong TE, Gao D, Chun J*, Kharchenko PV*, Zhang K*. Integrative single-cell analysis by transcriptional and epigenetic states in human adult brain. Nature Biotechnology (2017) doi:10.1038/nbt.4038
  3. Wang L*, Fan J*, Zhang CZ, Francis JM, Georghiou G, Hergert S, Shuqiang Li, Gambe R, Zhou CW, Yang C, Xiao S, Cin PD, Bowden M, Kotliar D, Shukla SA, Brown JR, Neuberg D, Alessi DR, Khachenko PV, Livak KJ, Wu CJ. Integrated single-cell genetic and transcriptional analysis suggests novel drivers of chronic lymphocytic leukemia. Genome Research (2017) doi:10.1101/gr.217331.116
  4. Wang L*, Brooks AN*, Fan J*, Wan Y*, Gambe R, Li S, Hergert S, Yin S, Freeman SS, Levin JZ, Fan L, Seiler M, Buonamici S, Smith PG, Chau KF, Cibulskis CL, Zhang W, Rassenti LZ, Ghia EM, Kipps TJ, Fernandes S, Bloch DB, Kotliar D, Landau DA, Shukla SA, Aster JC, Reed R, DeLuca DS, Brown JR, Neuberg D, Getz G, Livak KJ, Meyerson MM, Kharchenko PV, Wu CJ. Transcriptomic characterization of SF3B1 mutation reveals its pleiotropic effects in chronic lymphocytic leukemia. Cancer Cell (2016) doi: 10.1016/j.ccell.2016.10.005.
  5. Fan J, Salathia N, Liu R, Kaeser G, Yung Y, Herman J, Kaper F, Fan JB, Zhang K, Chun J, and Kharchenko PV. Characterizing transcriptional heterogeneity through pathway and gene set overdispersion analysis. Nature Methods (2016) doi: 10.1038/nmeth.3734

Additional Peer-Reviewed Publications

  1. Yin S, Gambe RG, Sun J, Martinez AZ, Cartun ZJ, Regis FFR, Wan Y, Fan J, Brooks AN, Herman SEM, Hacken ET, Taylor-Weiner A, Rassenti LZ, Ghia EM, Kipps TJ, Fleming MD, Ebert BL, Wistner A, Leshchiner I, DeCaprio JA, Getz G, Reed R, Carrasco RD, Wu CJ, Wang L. A Murine Model of Chronic Lymphocytic Leukemia Based on B Cell-Restricted Expression of Sf3b1 Mutation and Atm Deletion. Cancer Cell (2019) doi:10.1016/j.ccell.2018.12.013
  2. La manno G, Soldatov R, Zeisel A, Braun E, Hochgerner H, Petukhov V, Lidschreiber K, Kastriti ME, Lönnerberg P, Furlan A, Fan J, Borm LE, Liu Z, Bruggen DV, Guo J, He X, Barker R, Sundström S, Castelo-Branco G, Cramer P, Adameyko I, Linnarsson S, Kharchenko PV. RNA velocity of single cells. Nature (2018) doi:10.1038/s41586-018-0414-6
  3. Zhang X, Chen MH, Wu X, Kodani A, Fan J, Doan R, Ozawa M, Ma J, Yoshida N, Reiter JF, Black DL, Kharchenko PV, Sharp PA, Walsh CA. Cell-Type-Specific Alternative Splicing Governs Cell Fate in the Developing Cerebral Cortex. Cell (2016) doi:10.1016/j.cell.2016.07.025
  4. Burger JA*, Landau DA*, Taylor-Weiner A*, Bozic I*, Zhang H*, Sarosiek K, Wang L, Stewart C, Fan J, Hoellenriegel J, Sivina M, Dubuc AM, Fraser C, Han Y, Li S, Livak KJ, Zou L, Wan Y, Konoplev S, Sougnez C, Brown JR, Abruzzo LV, Carter SL, Keating MJ, Davids MS, Wierda WG, Cibulskis K, Zenz T, Werner L, Dal Cin P, Kharchencko P, Neuberg D, Kantarjian H, Lander E, Gabriel S, O’Brien S, Letai A, Weitz DA, Nowak MA, Getz G, Wu CJ. Clonal evolution in patients with chronic lymphocytic leukemia developing resistance to BTK inhibition. Nature Communications (2016) doi: 10.1038/ncomms11589
  5. Fan J, Slowikowski K. NAMCShiny: an interactive web application to explore health trends in 2003-2010 National Ambulatory Medical Care Survey data. HHPR (2015)
  6. Landau DA, Clement K, Ziller MJ, Boyle P, Fan J, Gu H, Stevenson K, Sougnez C, Wang L, Li S, Kotliar D, Zhang W, Ghandi M, Garraway L, Fernandes SM, Livak KJ, Gabriel S, Gnirke A, Lander ES, Brown JR, Neuberg D, Kharchenko PV, Hacohen N, Getz G, Meissner A and Wu CJ. Locally disordered methylation forms the basis of intratumor methylome variation in chronic lymphocytic leukemia. Cancer Cell (2014) doi: 10.1016/j.ccell.2014.10.012.
  7. Fan J, Yu Y, Meltzer PS, Cao L. Delineating the Role of BRF2 in Breast Cancer Pathogenesis. HURJ (2011)

Pre-prints

  1. Korsunsky I, Fan J, Slowikowski K, Zhang F, Wei K, Baglaenko Y, Brenner M, Loh PR, Raychaudhuri S. Fast, sensitive, and accurate integration of single cell data with Harmony. https://www.biorxiv.org/content/10.1101/461954v2
  2. Kwon H, Fan J, Kharchenko PV. Comparison of Principal Component Analysis and t-Stochastic Neighbor Embedding with Distance Metric Modifications for Single-cell RNA-sequencing Data Analysis. https://www.biorxiv.org/content/early/2017/01/29/102780
  3. Fan J, Fan D, Slowikowski K, Gehlenborg N, Kharchenko PV. UBiT2: a client-side web-application for gene expression data analysis. http://biorxiv.org/content/early/2017/03/22/118992

Book Chapters

  1. Fan J. Differential Pathway Analysis. Computational Methods for Single-Cell Data Analysis. Springer. 2019. ISBN 978-1-4939-9057-3.

SOFTWARE

Rstats

  • MERingue: R package for spatial correlation analysis for spatially-resolved transcriptomics data. https://jef.works/MERingue/
  • MUDAN: R package for multi-sample unified discriminant analysis. https://jef.works/MUDAN/
  • HoneyBADGER: R package for detecting copy number alteration from single-cell RNA-seq data. https://jef.works/HoneyBADGER/
  • SCDE/PAGODA: R package for single-cell differential expression and pathway over-dispersion analysis. https://bioconductor.org/packages/release/bioc/html/scde.html
  • brainmapr: R package to infer spatial location of subpopulations in the developing mouse brain by integrating single cell RNA-seq data with in situ hybridization data from the Allen Developing Atlas. https://github.com/hms-dbmi/brainmapr
  • LIGER: a light-weight R implementation of the Broad Gene Set Enrichment Analysis algorithm. https://cran.r-project.org/web/packages/liger/

Javascript

  • MERmaid: WebGL-based viewer for spatially-resolved transcriptomics data. http://jef.works/MERmaid/
  • UBiT2: user-friendly bioinformatics webtool for analyzing single cell transcriptomic data. https://jef.works/ubit2
  • tSNE-online: online web tool for t-SNE analysis. https://jef.works/tsne-online/

PRESENTATIONS

Invited Talks

  • Fan J. MERmaid - a React WebGL-Based Tool for Exploring Spatially Resolved Single-Cell Transcriptomics Data. Bio-IT World - Data Visualization and Exploration Tools. April 2019.
  • Fan J. Integrated genetic and transcriptional analysis at the single-cell level. Arizona State University. Molecular, Cellular and Tissue Bioengineering Symposium – Single Cell Technologies from Method Development to Application Bioengineering Symposium. April 2019.
  • Fan J. Spatial gene expression analysis in non-homogenous tissues. Department of Immunology Bioinformatics seminar. Nov 2018.
  • Fan J. Integrated genetic and transcriptional analysis at the single-cell level. Scangen. ISMB. July 2018.
  • Fan J. Computational and Statistical Methods for Characterizing Single-cell Heterogeneity. Research In Progress - Division of Pulmonary and Critical Care Medicine. Northwestern University. April 2018.
  • Fan J. Classifying and characterizing single cells using transcriptional and epigenetic analysis. Minisymposium - After the Data Deluge: Grappling with Transcriptional Complexity in the Brain. Society for Neuroscience. Nov 2017.
  • Fan J. CuSTEMized: Encouraging girls to see themselves in STEM. Pass-It-On Award winners panel. Grace Hopper Celebration. Oct 2017.
  • Fan J. Bioinformatics for Single Cell Analysis. Division of Immunology Bioinformatics Seminar. Aug 2017.
  • Fan J. Applying single cell transcriptomics - unraveling the complexity of the developing human brain. Festival of Genomics, Single Cell Genomics session. June 2016.
  • Fan J. Do art like a science. Do science like an art. TEDxJHU, Instructions Not Included. April 2016.
  • Fan J. JHU Young Alumni Leadership Symposium. March 2016.

Contributed Talks

  • Fan J, Kharchenko, PV. Linking genetic and transcriptional intratumoral heterogeneity at the single cell level. Broad Institute. Models, Inference, and Algorithms seminar series. May 2017.
  • Fan J, Salathia N, Liu R, Kaeser G, Yung Y, Herman J, Kaper F, Fan JB, Zhang K, Chun J, and Kharchenko PV. PAGODA - Pathway and gene set overdispersion analysis characterizes single cell transcriptional heterogeneity. Cold Spring Harbor. Single Cell Analysis Meeting, 2015.

Posters

  • Fan J, Lee H, Lee S, Ryu D, Lee S, Kim SJ, Kim K, Park PJ, Park WY, Kharchenko PV. Linking transcriptional and genetic tumor heterogeneity through allele analysis of single-cell RNA-seq data. Wellcome Genome Campus, Single Cell Genomics Conference. Sept 2016.
  • Fan J, Wang L, Brooks AN, Wan Y, Neuberg D, Rassenti K, Ghia E, Kipps T, Brown JR, Li S, Livak KJ, Meyerson MM, Kharchenko PV, Wu CJ. Comprehensive Bulk and Single Cell Transcriptomic Characterization of SF3B1 Mutation Reveals its Pleiotropic Effects in Chronic Lymphocytic Leukemia. American Society of Hematology, 57th Annual Meeting and Exhibition. Dec 2015.
  • Fan J, Lee HO, Lee S, Lee A, Park WY, Park PJ, Kharchenko PV. Hierarchical Bayesian Approach for CNV Detection from Single Cell RNA-seq Data. National Institutes of Health, Single Cell Investigators Meeting. April 2015.
  • Fan J, Salathia N, Liu R, Yung Y, Fan JB, Chun J, Zhang K, Kharchenko PV. Single Cell Differential Expression Identifies Neural Progenitor Subpopulations in the Developing Mouse Brain. National Institutes of Health, Single Cell Investigators Meeting, April 2014.
  • Fan J, Karchin R. Computational Assessment of the Utility of Limiting Orthologous Sequence Depth in Mutation Impact Prediction Performance. International Congress of Human Genetics/American Society of Human Genetics Conference. Oct 2011.

TEACHING & ADVISING

Teaching

Lead Instructor. The Innovation Institute, Newton, MA. Designed, wrote, and lead course curriculum for a classroom of 10 4th to 8th grade students. The year-long 2-hour weekly course exposed students to computer programming for the web using HTML, CSS, and Javascript.

  • Computer Programming for Future Entrepreneurs (2016-2017)
  • Computer Programming for Future Scientists and Engineers (2015-2016)

Teaching Fellow. Harvard Stem Cell Institute, Cambridge, MA. Designed, wrote, and lead lessons on single-cell analyses for ~50 students.

  • Single Cell Workshop (Nov 2015)
  • Single Cell Workshop (Oct 2014)

Teaching Assistant. Summer Institute in Biomedical Informatics, Harvard-MIT. Led discussions; supervised classes; mentored students. 20 undergraduates. (Summer 2016, Summer 2017)

Teaching Assistant. Introduction to Optimization, Johns Hopkins University, Baltimore, MD. Led multiple hands-on Matlab sessions and exam review workshops for 100s of students. Taught weekly sections and held office hours, assisted with grading homework and exams. (Fall 2012)

Research Advising

• Supervised 5 undergraduate and 1 high-school students, resulting in 3 publications.


AWARDS & HONORS

  • Anita Borg Pass-It-On Award Winner (2017)
  • BU GWISE Advocate of the Year (2017)
  • Regeneron “Dream Proposal” Prize Finalist (2017)
  • NSF MRS Outreach Award Recipient (2016)
  • ASH Abstract Achievement Award Recipient (2015)
  • Provost’s Undergraduate Research Award Winner (2012)
  • Intel Science Talent Search Semi-Finalist (2009)
  • Siemens Competition in Math, Science and Technology Semi-Finalist (2008)

PROFESSIONAL SERVICES

Journal reviewer (ad hoc)

  • Nature Communications
  • Nucleic Acids Research
  • PLOS ONE
  • PeerJ
  • F1000
  • Statistical Applications in Genetics and Molecular Biology

Administration and Conference Organizing

  • Organizer, WISE Beyond Your Years Symposium, HGWISE 10 year anniversary celebration (2015)

OUTREACH

Founder, Director, Lead Developer. CuSTEMized, a 501(c)3 non-profit organization that engages, encourages, and empowers young girls in Science, Technology, Engineering, and Math (STEM) by providing them with tangible products and educational experiences that foster a positive scientific identity from a young age. (2014-Current)

Co-Chair. Harvard Graduate Women in Science and Engineering HGWISE student group. (2013-2015)

Mentor-Scientist. Science Club for Girls SCFG for 2nd Graders, Boston, MA (2014-2015)

Undergraduate Mentor. Women in Science at Harvard-Radcliffe WISHR, Harvard College, Cambridge, MA (2013-2014)