Xiaojun Ren
Associate Professor
Department of Chemistry

Mailing Address:
Department of Chemistry
Campus Box 194, P.O. Box 173364
Denver, CO 80217-3364

Office Location:
Science Building
Room 4135

Expertise Areas:
Phase separation, Epigenetics, Chromatin, Genome organization, Single-molecule imaging

Education

1999—2002                        Ph.D. in Macromolecular Chemistry and Physics, Jilin University, P. R. China

1997—1999                        M.S. in Organic Chemistry, Department of Chemistry, Jilin University, P. R. China

1993—1997                        B.Eng. in Polymer Material Science and Engineering, Department of Chemistry, Jilin University, P. R. China

Professional Experience

2019—                                Associate Professor, Department of Chemistry, University of Colorado Denver

2012—2019                        Assistant Professor, Department of Chemistry, University of Colorado Denver

2005—2012                        Research Associate, HHMI/UM Ann Arbor

2002—2005                        Postdoctoral Fellow, Department of Chemistry, University of Cambridge UK

Academic Honors and Awards

2020                                    CU Denver Campus Award in Research and Creative Activities

2020                                    CU Denver CLAS Excellence in Research and Creative Activities Award

2019                                    The year in the Journal of Biological Chemistry: 2019

2017                                    CU Denver CLAS Excellence in Research and Creative Activities Award

2015                                    The Best of the Year Articles of the Journal of Biological Chemistry

2015                                    The Paper of the Week of the Journal of Biological Chemistry

2015                                    University (Downtown and Anschutz) Nomination for Pew Scholars

2002                                    Doctoral Degree with the Highest Honor

2002                                    The Distinguished Doctoral Dissertation Award

2001                                    Hong Kong Qiu Shi Graduate Scholarship

Professional Service

2020                                   Ad hoc NIH IMST-D (02) study section panel member

2020                                  Ad hoc NIH ZRG1 CBA (50) study section panel member

2020                                  Ad hoc NIH NCSD study section panel member

2019                                  Reviewer for NSF MCB Genetic Mechanisms

2018                                  Ad hoc NIH NCSD study section panel member

2018                                  Reviewer for Israel Science Foundation 

2012―present                  Reviewer for the following journals: PNAS, Science Advances, Nature Communications, Nature Metabolism, Epigenetics & Chromatin, Cancer Science, Nucleic Acid Research, Oncotarget, Theranostics, Briefings in Functional Genomics, Current Opinion in Genetics & Development, Chemical Communications, Sensors, Molecular BioSystems, Organic & Bimolecular Chemistry, Analytical Methods, Dalton Transactions, Medicinal Chemistry Communications, and Physical Chemistry Chemical Physics.

The Ren laboratory aims to develop and apply single-molecule techniques in epigenetics to studies of gene activities under physiological and pathological conditions​.

The Ren laboratory is funded by the National Institute of Health (R01s and R03) and the American Cancer Society. We are always looking for students, research assistants, and postdoctoral researchers who are highly motivated and exciting to discover knowledge. If you are interested in our research, please feel free to contact me (xiaojun.ren@ucdenver.edu).

The research in the Ren laboratory is focused on understanding the physicochemical principles that underpin how the gene expression programs are established and maintained under physiological and pathological conditions. We have discovered that epigenetic regulatory complexes phase-separate to assemble liquid droplets that facilitate gene regulation. We have developed and applied in vitro and in vivo single-molecule imaging to address fundamental questions in the epigenetic field. Our research is multidisciplinary across physical and life sciences.

We are working on the following projects:

1. Liquid-liquid phase separation links with the genome organization

How do cells spatially and temporally organize biochemical reactions to achieve functions is a fundamental question in biology. We study the roles of liquid-liquid phase separation of epigenetic regulatory complexes in gene expression programs. We have demonstrated that Polycomb proteins form microscopically visible, liquid-like condensates in cells. These condensates are assembled through liquid-liquid phase separation. These liquid droplets organize chromatin and accelerate the search of Polycomb proteins for their cognate sites.

a.Samantha Kent, Kyle Brown Chou-hsun Yang, Njood Alsaihati, Christina Tian, Haobin Wang, Xiaojun Ren (2020) Phase-separated Transcriptional Condensates Accelerate Target-search Process Revealed by Live-cell Single-molecule Imaging

Cell Reports 2020 Oct 13;33(2):108248. https://pubmed.ncbi.nlm.nih.gov/33053359/​

b.Roubina Tatavosian, Samantha Kent, Kyle Brown, Tingting Yao, Huy Nguyen Duc, Thao Ngoc Huynh, Chao Yu Zhen, Brian Ma, Haobin Wang, Xiaojun Ren (2019) Nuclear condensates of the Polycomb protein chromobox 2 (CBX2) assemble through phase separation.

Journal of Biological Chemistry 2019 Dec 4 Pubmed/30514760

c.Xiaojun Ren, Claudius Vincenz, Tom K Kerppola (2008) Changes in the distributions and dynamics of polycomb repressive complexes during embryonic stem cell differentiation.

Molecular and Cellular Biology 2008; 28 (9): 2884-2895 Pubmed/18316406

2. Single-molecule techniques in vitro and in vivo

We have developed and applied innovative single-molecule techniques to address questions of fundamental importance in the epigenetic/chromatin field, indicated by the following. (1) Live-cell single-molecule imaging: The binding and target-search kinetics is essential for understanding how chromatin-binding factors function. My research group developed and applied live-cell single-molecule tracking to quantify binding and target-search kinetics of epigenetic complexes in vivo. (2) Sm-ChIPi: The molecular composition and stoichiometry of epigenetic complexes on chromatin dictates functions of epigenetic complexes. My laboratory developed a new single-molecule chromatin immunoprecipitation imaging (Sm-ChIPi) approach that enables counting the number of epigenetic regulators on chromatin. Sm-ChIPi combines chromatin immunoprecipitation with single-molecule imaging. We use these state-of-the-art single-molecule techniques to address questions of fundamental importance in the epigenetic field that are not easily accessible by classical approaches.

a.Samantha Kent, Kyle Brown Chou-hsun Yang, Njood Alsaihati, Christina Tian, Haobin Wang, Xiaojun Ren (2020) Phase-separated Transcriptional Condensates Accelerate Target-search Process Revealed by Live-cell Single-molecule Imaging

Cell Reports 2020 Oct 13;33(2):108248. https://pubmed.ncbi.nlm.nih.gov/33053359/​

b.Roubina Tatavosian, Huy Nguyen Duc, Thao Ngoc Huynh, Dong Fang, Benjamin Schmitt, Xiaodong Shi, Yiming Deng, Christopher Phiel, Tingting Yao, Zhiguo Zhang, Haobin Wang, Xiaojun Ren (2018) Live-cell single-molecule dynamics of PcG proteins imposed by the DIPG H3.3K27M mutation.

Nature Communications 2018 May 25; 9(1):2080 Pubmed/29802243

c.Chao Yu Zhen, Roubina Tatavosian, Thao Ngoc Huynh, Huy Nguyen Duc, Raibatak Das, Marko Kokotovic, Jonathan B Grimm, Luke D Lavis, Jun Lee, Frances J Mejia, Yang Li, Tingting Yao, Xiaojun Ren (2016) Live-cell single-molecule tracking reveals co-recognition of H3K27me3 and DNA targets polycomb Cbx7-PRC1 to chromatin.

eLIFE 2016 Oct 10; 5. pii: e17667 Pubmed/27723458   

d.Roubina Tatavosian, Chao Yu Zhen, Huy Nguyen Duc, Maggie M Balas, Aaron M Johnson, Xiaojun Ren (2015) Distinct Cellular Assembly Stoichiometry of Polycomb Complexes on Chromatin Revealed by Single-molecule Chromatin Immunoprecipitation Imaging.

Journal of Biological Chemistry 2015 Nov 20; 290(47):28038-54 Pubmed/26381410

3. Defining the mechanisms underlying diffuse intrinsic pontine gliomas

Diffuse intrinsic pontine gliomas (DIPGs) are highly aggressive and difficult to treat brain tumors. DIPGs exhibit a characteristic mutation of lysine 27 to methionine (K27M) in genes encoding histone H3. H3K27 (the native protein) and its modification are the substrate of Polycomb proteins. How the H3K27M mutation affects the functioning of Polycomb remains controversial. By combining live-cell single-molecule imaging and genetic engineering, we have uncovered a novel molecular mechanism underlying the oncogenic H3K27M mutation; it alters the target-search kinetics of Polycomb proteins, which in turn affects their functions. Furthermore, we have pointed out a potential therapeutic target for improvement of DIPG treatment. Our results suggest that the reduced “sampling” frequency of Polycomb proteins for target sites, by prolonging its search process, reprograms the genomic occupancy of Polycomb proteins, which is a new insight into the reprogramming of epigenome by a cancer mutation in vivo.

a.Roubina Tatavosian, Huy Nguyen Duc, Thao Ngoc Huynh, Dong Fang, Benjamin Schmitt, Xiaodong Shi, Yiming Deng, Christopher Phiel, Tingting Yao, Zhiguo Zhang, Haobin Wang & Xiaojun Ren (2018) Live-cell single-molecule dynamics of PcG proteins imposed by the DIPG H3.3K27M mutation.

      Nature Communications 2018 May 25; 9(1):2080 Pubmed/29802243

Selected publications since independence

#indicates the corresponding author

Samantha Kent, Kyle Brown Chou-hsun Yang, Njood Alsaihati, Christina Tian, Haobin Wang, Xiaojun Ren# (2020) Phase-separated Transcriptional Condensates Accelerate Target-search Process Revealed by Live-cell Single-molecule Imaging
Cell Reports 2020 Oct 13;33(2):108248.

Roubina Tatavosian, Samantha Kent, Kyle Brown, Tingting Yao, Huy Nguyen Duc, Thao Ngoc Huynh, Chao Yu Zhen, Brian Ma, Haobin Wang, Xiaojun Ren# (2019) Nuclear condensates of the Polycomb protein chromobox 2 (CBX2) assemble through phase separation
Journal of Biological Chemistry Feb 1;294(5):1451-1463. 
“The year in JBC” for 2019

Roubina Tatavosian, Thao Ngoc Huynh, Huy Nguyen Duc, Dong Fang, Benjamin Schmitt, Christopher Phiel, Tingting Yao, Zhiguo Zhang, Haobin Wang, Xiaojun Ren# (2018) Live-cell Single-Molecule Dynamics of PcG Proteins Imposed by the DIPG H3.3K27M Mutation
Nature Communications 9 (1), 2080

Roubina Tatavosian, Xiaojun Ren# (2018) Sm-ChIPi: Single-Molecule Chromatin Immunoprecipitation Imaging
Methods Mol Biol.1689:113-126

Chao Yu Zhen, Roubina Tatavosian, Thao Ngoc Huynh, Huy Nguyen Duc, Raibatak Das, Marko Kokotovic, Jonathan B Grimm, Luke D Lavis, Jun Lee, Frances J Mejia, Yang Li, Tingting Yao, Xiaojun Ren# (2016) Live-cell single-molecule tracking reveals co-recognition of H3K27me3 and DNA targets Polycomb Cbx7-PRC1 to chromatin 
eLIFE Oct 10;5. pii: e17667

Roubina Tatavosian&, Chao Yu Zhen&, Huy Nguyen Duc&, Maggie M. Balas, Aaron Johnson, Xiaojun Ren# (2015) Distinct Cellular Assembly Stoichiometry of Polycomb Complexes on Chromatin Revealed by Single-Molecule Chromatin Immunoprecipitation Imaging
Journal of Biological Chemistry 290(47):28038-54
The Best of the Year article of JBC in Gene Regulation 2015
J Biol Chem: Most-Read Full-Text Articles
ASBMB January member news
JBC Podcasts
Development of new imaging to analyze the binding mechanisms of epigenetic complexes

Colleen M. Bartmana, Jennifer Egelstona, Xiaojun Ren, Raibatak Dasa, Christopher J. Phiel (2015) A simple and efficient method for transfecting mouse embryonic stem cells using polyethylenimine
Experimental Cell Research 330(1):178-85

Chao Yu Zhen&, Huy Nguyen Duc&, Marko Kokotovic&, Christopher Phiel, Xiaojun Ren#(2014) Cbx2 stably associates with mitotic chromosomes via a PRC2 or PRC1-independent mechanism and is needed for recruiting PRC1 complex to mitotic chromosomes
Molecular Biology of the Cell 25(23):3726-39

Bo Cheng*, Xiaojun Ren*, Tom K Kerppola (2014) KAP1 represses differentiation-inducible genes in embryonic stem cells through cooperative binding with PRC1 and derepresses pluripotency-associated genes
Molecular and Cellular Biology 34(11):2075-91
(*Contributed equally to this work)
One of the most read articles in May, 2014

A complete list of publications

CHEM 5810-Graduate Biochemistry I

CHEM 5830-Graduate Biochemistry II

CHEM 4835/5835-Biochemistry of Gene Regulation and Cancer

CHEM 4828-Biochemistry Laboratory

CHEM 5610-Understanding & Presenting Chemical Research

CHEM 3498-Honors Organic Chemistry Lab II