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Joshua Black, PhD

Assistant Professor


Contact Information:

University of Colorado Denver
Department of Pharmacology
Mail Stop 8303, RC1-North
12801 East 17th Ave
Aurora CO 80045

Phone: (303) 724-9991
Fax: (303) 724-3663
Office: RC1-North, P18-6116

Affiliated Programs

 

​​
​Genome instability, chromosomal structural aberrations, and copy number variation are 
hallmarks of cancer.  Recent advances in sequencing technology have uncovered a large amount 
of intra-tumoral heterogeneity in both gene expression and chromosomal copy number across a 
range of tumors. These aberrations are often thought of as integrated and inherited genetic events 
within tumors.   However, new analyses are beginning to demonstrate that some copy number 
heterogeneity may not be stably inherited.  We identified the first enzyme capable of modulating 
site-specific copy gains and established that the localized chromatin states impact the propensity 
of a region to undergo rereplication and copy gain. This work established a role for epigenetic 
regulators and chromatin states in regulating copy number heterogeneity. Furthermore, we 
established that physiological signals such as hypoxia promote site-specific copy gains of drug 
resistant oncogenes, which can contribute to drug resistance. This new perspective on cancer 
genetics helps explain copy number heterogeneity in tumors and has important clinical 
implications for characterizing and treating drug resistant cancer. 
My laboratory is expanding on these findings to: 1) Identify new targets for site-specific copy 
gain that mediate important cancer phenotypes and characterize the chromatin pathways that 
regulate them, 2) Conduct screens to identify regulators of DNA re-replication and site-specific 
copy gain, 3) Determine how site-specific copy gain contributes to drug resistance, 4) 
Characterize the molecular nature of regions that undergo site-specific copy gain.

Professional Research Assistant, Graduate Student, and Postdoctoral Fellow positions available.
​Selected Publications:

1. Black JC, Whetstine JR.  (2015)  Too little O2, Too much gain.  Cell Cycle. 14(18):2869-2870.  
PMID:26221746

2. Black JC*, Atabakhsh E*, Kim J*, Biette KM, Van Rechem C, Ladd B, Burrowes PD, Donado C, 
Mattoo H, Kleinstiver BP, Song B, Andriani G, Joung JK, Iliopoulos O, Montagna C, Pillai S, Getz 
G, Whetstine JR. (2015) Hypoxia drives transient site-specific copy gain drug-resistant gene 
expression.  Genes and Development. 29(10):1018-1031.  PMID: 25995187

3. Black JC*, Manning A*, Van Rechem C*, Kim J*, Ladd B, Cho J, Pineda CM, Murphy N, Daniels 
DL, Montagna C, Lewis PW, Glass K, Allis CD, Dyson NJ, Getz G, Whetstine JR.  (2013) 
H3K9/36me3 Lysine Demethylase KDM4A Induces Site-Specific Copy Gain and Re-replication of 
Regions Amplified in Tumors.  Cell.  154(3):541-555.  PMID 23871696 * These authors contributed equally to this work.

4. Black JC, Van Rechem C, Whetstine JR.  (2012) Histone Lysine Methylation Dynamics: 
Establisment, Regulation, and Biological Impact.  Mol. Cell.  48(4):491-507.  PMID 23200123

5. Black JC, Allen A, Van Rechem C, Forbes E, Longworth M, Tschöp K, Rinehart C, Quiton J, 
Walsh R, Smallwood A, Dyson NJ, Whetstine JR. (2010)  Molecular Cell.  40(5):736-48.  PMID 
21145482.