Kevin C. Wang, M.D., Ph.D., is an Assistant Professor of Dermatology, former director of the inpatient dermatology consult service at Stanford, and Attending Physician at the Palo Alto VA. He is a Faculty Member in the Program in Epithelial Biology, Bio-X, and Cancer Biology Ph.D. Program, and his research focuses on epigenetic mechanisms of gene regulation in stem cells, development, and cancer. His clinical interests include complex adult medical dermatology, pruritus, neuropathic dermatoses, and inpatient dermatology.
- Complex Medical Dermatology
- Inpatient Dermatology
- Pruritus (Itching)
- Neuropathic/Neurogenic Dermatosis
Fellowship: Stanford University Hospital and Clinics - Dermatology Department (2010) CA
Residency: UCSF (2009) CA
Internship: Brigham and Women's Hospital Harvard Medical School (2006) MA
Professional Education: Harvard Medical School (2003) MA
Board Certification: Dermatology, American Board of Dermatology (2009)
Medical Education: UCSF (2005) CA
Current Research and Scholarly Interests
The Wang lab takes an interdisciplinary approach to studying fundamental mechanisms controlling gene expression in mammalian cells, and how epigenetic mechanisms such as DNA methylation, chromatin modifications, and RNA influence chromatin dynamics to affect gene regulation.
- Cancer Biology Journal Club
CBIO 280 (Spr)
- Molecular and Genetic Basis of Cancer
CBIO 240 (Aut)
Independent Studies (8)
- Directed Reading in Cancer Biology
CBIO 299 (Win, Spr)
- Directed Reading in Dermatology
DERM 299 (Aut, Win, Spr)
- Early Clinical Experience in Dermatology
DERM 280 (Aut, Win, Spr, Sum)
- Graduate Research
CBIO 399 (Aut, Win, Spr, Sum)
- Graduate Research
DERM 399 (Win, Spr)
- Medical Scholars Research
DERM 370 (Aut, Win, Spr)
- Teaching in Cancer Biology
CBIO 260 (Spr)
- Undergraduate Research
DERM 199 (Aut, Win, Spr, Sum)
- Directed Reading in Cancer Biology
- Prior Year Courses
Graduate and Fellowship Programs
Essential role of lncRNA binding for WDR5 maintenance of active chromatin and embryonic stem cell pluripotency.
The WDR5 subunit of the MLL complex enforces active chromatin and can bind RNA; the relationship between these two activities is unclear. Here we identify a RNA binding pocket on WDR5, and discover a WDR5 mutant (F266A) that selectively abrogates RNA binding without affecting MLL complex assembly or catalytic activity. Complementation in ESCs shows that WDR5 F266A mutant is unable to accumulate on chromatin, and is defective in gene activation, maintenance of histone H3 lysine 4 trimethylation, and ESC self renewal. We identify a family of ESC messenger and lncRNAs that interact with wild type WDR5 but not F266A mutant, including several lncRNAs known to be important for ESC gene expression. These results suggest that specific RNAs are integral inputs into the WDR5-MLL complex for maintenance of the active chromatin state and embryonic stem cell fates. DOI: http://dx.doi.org/10.7554/eLife.02046.001.
View details for DOI 10.7554/eLife.02046
View details for PubMedID 24521543
- Training the Contemporary Surgeon-Scientist PLASTIC AND RECONSTRUCTIVE SURGERY 2012; 129 (4): 1023-1025
Molecular Mechanisms of Long Noncoding RNAs
2011; 43 (6): 904-914
Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. Here we discuss the emerging archetypes of molecular functions that lncRNAs execute-as signals, decoys, guides, and scaffolds. For each archetype, examples from several disparate biological contexts illustrate the commonality of the molecular mechanisms, and these mechanistic views provide useful explanations and predictions of biological outcomes. These archetypes of lncRNA function may be a useful framework to consider how lncRNAs acquire properties as biological signal transducers and hint at their possible origins in evolution. As new lncRNAs are being discovered at a rapid pace, the molecular mechanisms of lncRNAs are likely to be enriched and diversified.
View details for DOI 10.1016/j.molcel.2011.08.018
View details for PubMedID 21925379
Crystal structure of the N-terminal region of human Ash2L shows a winged-helix motif involved in DNA binding
2011; 12 (8): 797-803
Ash2L is a core component of the MLL family histone methyltransferases and has an important role in regulating the methylation of histone H3 on lysine 4. Here, we report the crystal structure of the N-terminal domain of Ash2L and reveal a new function of Ash2L. The structure shows that Ash2L contains an atypical PHD finger that does not have histone tail-binding activity. Unexpectedly, the structure shows a previously unrecognized winged-helix motif that directly binds to DNA. The DNA-binding-deficient mutants of Ash2L reduced Ash2L localization to the HOX locus. Strikingly, a single mutation in Ash2L(WH) (K131A) breaks the chromatin domain boundary, suggesting that Ash2L also has a role in chromosome demarcation.
View details for DOI 10.1038/embor.2011.101
View details for Web of Science ID 000293326500014
View details for PubMedID 21660059
View details for PubMedCentralID PMC3147254
A long noncoding RNA maintains active chromatin to coordinate homeotic gene expression
2011; 472 (7341): 120-U158
The genome is extensively transcribed into long intergenic noncoding RNAs (lincRNAs), many of which are implicated in gene silencing. Potential roles of lincRNAs in gene activation are much less understood. Development and homeostasis require coordinate regulation of neighbouring genes through a process termed locus control. Some locus control elements and enhancers transcribe lincRNAs, hinting at possible roles in long-range control. In vertebrates, 39 Hox genes, encoding homeodomain transcription factors critical for positional identity, are clustered in four chromosomal loci; the Hox genes are expressed in nested anterior-posterior and proximal-distal patterns colinear with their genomic position from 3' to 5'of the cluster. Here we identify HOTTIP, a lincRNA transcribed from the 5' tip of the HOXA locus that coordinates the activation of several 5' HOXA genes in vivo. Chromosomal looping brings HOTTIP into close proximity to its target genes. HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. Induced proximity is necessary and sufficient for HOTTIP RNA activation of its target genes. Thus, by serving as key intermediates that transmit information from higher order chromosomal looping into chromatin modifications, lincRNAs may organize chromatin domains to coordinate long-range gene activation.
View details for DOI 10.1038/nature09819
View details for PubMedID 21423168
- Neurogenic Rosacea: A Distinct Clinical Subtype Requiring a Modified Approach to Treatment ARCHIVES OF DERMATOLOGY 2011; 147 (1): 123-126
Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis
2010; 464 (7291): 1071-U148
Large intervening non-coding RNAs (lincRNAs) are pervasively transcribed in the genome yet their potential involvement in human disease is not well understood. Recent studies of dosage compensation, imprinting, and homeotic gene expression suggest that individual lincRNAs can function as the interface between DNA and specific chromatin remodelling activities. Here we show that lincRNAs in the HOX loci become systematically dysregulated during breast cancer progression. The lincRNA termed HOTAIR is increased in expression in primary breast tumours and metastases, and HOTAIR expression level in primary tumours is a powerful predictor of eventual metastasis and death. Enforced expression of HOTAIR in epithelial cancer cells induced genome-wide re-targeting of Polycomb repressive complex 2 (PRC2) to an occupancy pattern more resembling embryonic fibroblasts, leading to altered histone H3 lysine 27 methylation, gene expression, and increased cancer invasiveness and metastasis in a manner dependent on PRC2. Conversely, loss of HOTAIR can inhibit cancer invasiveness, particularly in cells that possess excessive PRC2 activity. These findings indicate that lincRNAs have active roles in modulating the cancer epigenome and may be important targets for cancer diagnosis and therapy.
View details for DOI 10.1038/nature08975
View details for Web of Science ID 000276635000045
View details for PubMedID 20393566
View details for PubMedCentralID PMC3049919
Regeneration, repair and remembering identity: the three Rs of Hox gene expression
TRENDS IN CELL BIOLOGY
2009; 19 (6): 268-275
Hox genes encode transcription factors that specify embryonic positional identity in cells and guide tissue differentiation. Recent advances have greatly increased our understanding of the epigenetic mechanisms that ensure the faithful expression of Hox genes in adult cells and which involve the interplay of histone methylation, demethylation and intergenic transcription of long non-coding RNAs. The transcriptional memory of Hox genes poses both an opportunity and a challenge for regenerative medicine. Matching the positional identity of transplanted stem cells with that of the host environment, as reflected by their respective Hox profiles, is likely to be required to achieve regenerative healing. Strategies to manipulate the plasticity of Hox gene expression will probably become a major focus in regenerative medicine.
View details for DOI 10.1016/j.tcb.2009.03.007
View details for PubMedID 19428253
Recent advances in acne vulgaris research: insights and clinical implications.
Advances in dermatology
2008; 24: 197-209
Understanding of acne vulgaris has taken major steps forward over the past few years. The renewed interest in the effect of dietary interventions on acne, the elucidation of the involvement of TLR and MMPs in acne pathogenesis, and a more detailed functional understanding of various treatment modalities at the molecular level are all promising indications that advances in therapeutics are sure to follow. Health utilities will serve not only as powerful outcome measures of treatment effects but also as clinical decision-making aids in everyday practice. It is hoped that future advances will further uncover additional molecular and cellular details of pathophysiology, leading to rational targeted design of medications, and advance clinical management through improved understanding of the psychosocial impact of acne on patients.
View details for PubMedID 19256310
Images in clinical medicine. Koplik's spots.
New England journal of medicine
2006; 354 (7): 740-?
View details for PubMedID 16481641
PKC mediates inhibitory effects of myelin and chondroitin sulfate proteoglycans on axonal regeneration
2004; 7 (3): 261-268
Successful axon regeneration in the mammalian central nervous system (CNS) is at least partially compromised due to the inhibitors associated with myelin and glial scar. However, the intracellular signaling mechanisms underlying these inhibitory activities are largely unknown. Here we provide biochemical and functional evidence that conventional isoforms of protein kinase C (PKC) are key components in the signaling pathways that mediate the inhibitory activities of myelin components and chondroitin sulfate proteoglycans (CSPGs), the major class of inhibitors in the glial scar. Both the myelin inhibitors and CSPGs induce PKC activation. Blocking PKC activity pharmacologically and genetically attenuates the ability of CNS myelin and CSPGs to activate Rho and inhibit neurite outgrowth. Intrathecal infusion of a PKC inhibitor, Gö6976, into the site of dorsal hemisection promotes regeneration of dorsal column axons across and beyond the lesion site in adult rats. Thus, perturbing PKC activity could represent a therapeutic approach to stimulating axon regeneration after brain and spinal cord injuries.
View details for DOI 10.1038/nn1193
View details for Web of Science ID 000189197900016
View details for PubMedID 14770187
p75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp
2002; 420 (6911): 74-78
In inhibiting neurite outgrowth, several myelin components, including the extracellular domain of Nogo-A (Nogo-66), oligodendrocyte myelin glycoprotein (OMgp) and myelin-associated glycoprotein (MAG), exert their effects through the same Nogo receptor (NgR). The glycosyl phosphatidylinositol (GPI)-anchored nature of NgR indicates the requirement for additional transmembrane protein(s) to transduce the inhibitory signals into the interior of responding neurons. Here, we demonstrate that p75, a transmembrane protein known to be a receptor for the neurotrophin family of growth factors, specifically interacts with NgR. p75 is required for NgR-mediated signalling, as neurons from p75 knockout mice are no longer responsive to myelin and to each of the known NgR ligands. Blocking the p75-NgR interaction also reduces the activities of these inhibitors. Moreover, a truncated p75 protein lacking the intracellular domain, when overexpressed in primary neurons, attenuates the same set of inhibitory activities, suggesting that p75 is a signal transducer of the NgR-p75 receptor complex. Thus, interfering with p75 and its downstream signalling pathways may allow lesioned axons to overcome most of the inhibitory activities associated with central nervous system myelin.
View details for DOI 10.1038/nature01176
View details for Web of Science ID 000179068100039
View details for PubMedID 12422217
Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth
2002; 417 (6892): 941-944
The inhibitory activity associated with myelin is a major obstacle for successful axon regeneration in the adult mammalian central nervous system (CNS). In addition to myelin-associated glycoprotein (MAG) and Nogo-A, available evidence suggests the existence of additional inhibitors in CNS myelin. We show here that a glycosylphosphatidylinositol (GPI)-anchored CNS myelin protein, oligodendrocyte-myelin glycoprotein (OMgp), is a potent inhibitor of neurite outgrowth in cultured neurons. Like Nogo-A, OMgp contributes significantly to the inhibitory activity associated with CNS myelin. To further elucidate the mechanisms that mediate this inhibitory activity of OMgp, we screened an expression library and identified the Nogo receptor (NgR) as a high-affinity OMgp-binding protein. Cleavage of NgR and other GPI-linked proteins from the cell surface renders axons of dorsal root ganglia insensitive to OMgp. Introduction of exogenous NgR confers OMgp responsiveness to otherwise insensitive neurons. Thus, OMgp is an important inhibitor of neurite outgrowth that acts through NgR and its associated receptor complex. Interfering with the OMgp/NgR pathway may allow lesioned axons to regenerate after injury in vivo.
View details for Web of Science ID 000176441200037
View details for PubMedID 12068310
Knowing how to navigate: mechanisms of semaphorin signaling in the nervous system.
Science's STKE : signal transduction knowledge environment
2002; 2002 (119): re1-?
Neuronal connections are made during embryonic development with astonishing precision to ultimately form the physical basis for the central nervous system's main capacity: information processing. Over the past few decades, much has been learned about the general principles of axon guidance. A key finding to emerge is that extracellular cues play decisive roles in establishing the connections. One family of such cues, the semaphorin proteins, was first identified as repellents for navigating axons during brain wiring. Recent studies have implicated these molecules in many other processes of neuronal development, including axonal fasciculation, target selection, neuronal migration, and dendritic guidance, as well as in the remodeling and repair of the adult nervous system. It appears that responding neuronal processes sense these semaphorin signals by a family of transmembrane molecules, namely the plexins, even though neuropilins were also found to be required for mediating the interaction between plexins and class 3 semaphorins. Our understanding of the intracellular signaling machinery linking the receptors to the cytoskeleton machinery is still incomplete, but several molecules have been implicated in mediating or modulating semaphorin-induced responses. Adding to the complexity of semaphorin biology, new findings implicate semaphorins in functioning not only as signaling ligands, but also as signal-transducing receptors. Thus, semaphorins may serve as important probes for exploring the mechanisms of intercellular communication during the development and function of the nervous system.
View details for PubMedID 11842242