Howard Y. Chang

Clinical Focus

• Dermatology

Administrative Appointments

• Program Committee, Cancer Biology (2005 - present)

Honors and Awards

• Elected Member, American Society for Clinical Investigation (2009)
• Vilcek Prize for Creative Promise, Vilcek Foundation (2009)
• New Faculty Award, California Institute for Regenerative Medicine (2008-2013)
• Research Scholar Award, American Cancer Society (2007-2010)
• Scholar Award, Damon Runyon Cancer Research Foundation (2006-2008)

Professional Education

Postdoctoral Advisees

Rajnish Gupta, Miao-Chih Tsai, David Wong

Graduate & Fellowship Program Affiliations

• Cancer Biology
• Dermatology

Web Site Links

• Chang Lab, Stanford University

Research Interests

We are interested in two fundamental questions in epithelial biology: (1) the basis of positional identities in epidermal structures throughout the body, and (2) how those signals and boundaries may be abrogated to allow cancer metastasis. Although site-specific differences in epidermal structures (such as hairs on skin) on different anatomic sites are easily appreciated and are the basis of many diagnostic and treatment strategies in skin diseases, embryologic transplantation experiments have demonstrated that it is the underlying mesenchymal stroma that dictates the epithelial fates that develop. We have begun to define the organizational and developmental principles of stromal cells based on their global gene expression programs. For example, we discovered that endothelial cell (EC) diversity is primarily dictated by the vessel size of origin, and the Notch-Hey2 and left-right polarity signaling axis help to specify artery vs. vein fate. In contrast, fibroblasts from each anatomic site exhibit systematic and characteristic differences in gene expression and retain the embryonic anatomic expression pattern of Hox genes. Fibroblasts are thus excellent candidates as the bearer of positional memory in tissues and organs.

The unanticipated diversity and precision of fibroblast differentiation suggest much richer roles for stroma cells during development and diverse disease processes. Taking advantage of the unique capacities of skin for primary cell culture, gene transfer, and tissue reconstitution of site-specific features, we are pursuing the mechanisms by which the Hox code in fibroblasts specify epidermal fates, and how the embryonic Hox code is maintained in isolated adult fibroblasts.

In contrast to the orderly acquisition of positional identities in development, cancer cells can abrogate and override the positional cues in tissues and organs as they metastasize. We discovered that one way that cancer cells may accomplish this feat is by activation...

Publications

• SIRT6 links histone H3 lysine 9 deacetylation to NF-kappaB-dependent gene expression and organismal life span. Kawahara TL, Michishita E, Adler AS, Damian M, Berber E, Lin M, McCord RA, Ongaigui KC, Boxer LD, Chang HY, Chua KF. Cell. 2009; 136 (1): 62-74
• Module map of stem cell genes guides creation of epithelial cancer stem cells. Wong DJ, Liu H, Ridky TW, Cassarino D, Segal E, Chang HY. Cell Stem Cell. 2008; 2 (4): 333-44
• A dermal HOX transcriptional program regulates site-specific epidermal fate. Rinn JL, Wang JK, Allen N, Brugmann SA, Mikels AJ, Liu H, Ridky TW, Stadler HS, Nusse R, Helms JA, Chang HY. Genes Dev. 2008; 22 (3): 303-7
• Functional demarcation of active and silent chromatin domains in human HOX loci by noncoding RNAs. Rinn JL, Kertesz M, Wang JK, Squazzo SL, Xu X, Brugmann SA, Goodnough LH, Helms JA, Farnham PJ, Segal E, Chang HY. Cell. 2007; 129 (7): 1311-23
• Genetic regulators of large-scale transcriptional signatures in cancer. Adler AS, Lin M, Horlings H, Nuyten DS, van de Vijver MJ, Chang HY. Nat Genet. 2006; 38 (4): 421-30