Howard Y. Chang
Academic Appointments
- Professor, Dermatology
- Member, Bio-X
- Member, Stanford Cancer Institute
Key Documents
Contact Information
-
Clinical Offices
Dermatology Clinic - North Campus 450 Broadway Street Pavilion B Redwood City, CA 94063 Tel Work (650) 723-6316 Fax (650) 721-3476Practices at Stanford Hospital and Clinics and Lucile Packard Children's Hospital
- Academic Offices
Alternate Contact Ray Herrman Administrative Associate Email Tel Work 650-725-7022Not for medical emergencies or patient use
Professional Overview
Clinical Focus
- Cancer> Cutaneous (Dermatologic) Oncology
- Dermatology
- General Dermatology
Administrative Appointments
- Program Committee, Cancer Biology (2005 - 2012)
Honors and Awards
- Alfred Marchionini Research Prize, Alfred Marchionini Foundation (2011)
- CE.R.I.E.S. Award, Chanel Research and Technology (2010)
- Early Career Scientist, Howard Hughes Medical Institute (2009-2015)
- 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)
Professional Education
| Residency: | Stanford University School of Medicine CA (2003) |
| Medical Education: | Harvard Medical School MA (2000) |
| Board Certification: | Dermatology, American Board of Dermatology (2004) |
| Internship: | Santa Clara Valley Medical Center, CA USA (2001) |
| Ph.D.: | MIT, Biology (1998) |
| A.B.: | Harvard, Biochemistry (1994) |
Postdoctoral Advisees
Ye Chen, Pedro De Oliveira Rodrigues Batista, Paul Giresi, Lingjie Li, Robert Spitale, Kevin Wang, Lisa Zaba, Qiangfeng Zhang, Xinying Zheng
Graduate & Fellowship Program Affiliations
Internet Links
Scientific Focus
Current Research Interests
The same genetic blueprint gives rise to thousands of cell types that make up the human body. Intricate mechanisms govern the choice to make skin, heart, or brain cells. These different cell types must be correctly arranged in spatial patterns to make functioning tissues and organs. In many organisms with continual turnover of cells, the genome faces the additional challenge of ensuring the faithful transmission of information throughout a lifetimeover decades in the case of humans. Thus, how one genome encodes thousands of patterns in space and time is of central importance to biology and medicine. Inappropriate activation of genes can give rise to birth defects, premature aging, or cancer, among many other diseases. Restoration of proper organ function often requires restoring homeostatic gene regulation.
Long Noncoding RNAs and Positional Identity
As a practicing dermatologist, I am fascinated by what makes human skin from different parts of the body different, a fact that guides the diagnosis and treatment of many skin diseases. Why do long hairs grow on the scalp but not on our palms or soles? How do cells know where they are located in the body, and how do they remember this information?
We discovered that one class of skin cells, the fibroblasts, encode the positional identity of skin via specific markings on their chromatin, the DNA-protein complex where genes reside. Based on the chromatin configurations of specific genes, most notably the HOX genes, fibroblasts differentially activate hundreds of genes based on their the cells location along three anatomic axesanterior-posterior (head to tail), proximal-distal (close or far away from the trunk), and dermal-nondermal (surface or internal organ). This in effect creates a global positioning system for all cells to navigate.
These studies also revealed a surprising abundance of long intergenic long noncoding RNAs (also known as lincRNAs, a newly recognized type of genes that do not code forencode proteins) that are involved in programming chromatin states. We are particularly fascinated by HOTAIR, the first known lincRNA that can regulate the chromatin state of genes on distantly located chromosomes. We now appreciate that the genome is pervasively transcribed to give rise to thousands of lincRNAs, which are likely to play key roles in the gene regulation of diverse biological states and disease. We are interested in understanding how lincRNAs control gene activity, and in deciphering the rules that will allow the functions of thousands of lincRNAs to be predicted and studied.
Large-Scale Gene Regulatory Programs in Cancer Metastasis and Self-Renewal
In contrast to the orderly acquisition of positional identity, cancer progression is characterized by abrogation of normal positional boundaries, especially in metastasis, which is the leading cause of cancer death. We and many others have previously identified gene expression signatures (GES ), composed of dozens to hundreds of genes, that distinguish indolent human cancers from those prone to metastasis; these signatures can provide improved prognostic prediction for cancer patients. Furthermore, we have developed methods to pinpoint master regulators of GESsingular control points that can toggle the activity of the entire genetic program. This allows complex gene programs observed in human cancers to be easily recapitulated in the laboratory as models for drug development. This has enabled the creation of faithful laboratory models of human cancer types, identified specific drugs that can target these cancers, and revealed the hierarchy of transcriptional programs involved in the generation of cancer stem cellsthe cells that continually repopulate a tumor or its metastases.
Publications
- Control of somatic tissue differentiation by the long non-coding RNA TINCR. Nature. 2013; (7431): 231-5
- Long noncoding RNAs: cellular address codes in development and disease. Cell. 2013; (6): 1298-307
- RNA SHAPE analysis in living cells. Nat Chem Biol. 2013; (1): 18-20
- Aging, rejuvenation, and epigenetic reprogramming: resetting the aging clock. Cell. 2012; (1-2): 46-57
- A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression. Nature. 2011; (7341): 120-4
- Extensive and coordinated transcription of noncoding RNAs within cell-cycle promoters. Nat Genet. 2011; (7): 621-9
Help