Paul Khavari

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Paul A. Khavari is the Carl J. Herzog Professor [1] at the Stanford University School of Medicine and the Founding Co-Director of the Stanford Program in Epithelial Biology. [2] He is an elected member of the National Academy of Medicine. [3]

Contents

The Khavari Laboratory uses multiomic and computational approaches to study stem cell differentiation, cancer, and the genomics of common polygenic human diseases.

Education

Khavari studied biology and history at Stanford University then earned an MD at Yale School of Medicine. [4] He did research at the Brigham and Women's Hospital [4] and Harvard Medical School before undertaking Dermatology residency training at Yale. [5] He completed PhD studies in the laboratory of Gerald Crabtree at the Stanford University School of Medicine. [6]

Academic career

Khavari joined the Stanford faculty in 1993, [7] and began service as Chief of Dermatology at the VA Palo Alto Healthcare System. [7] [8] In 1999, he co-founded the Stanford Program in Epithelial Biology with Dr. Tony Oro and has served as Co-Director since. [9] In 2010, he was appointed Chair of the Stanford University School of Medicine Department of Dermatology, [10] a leading dermatology department globally. He was one of three Stanford faculty members elected to the Institute of Medicine (now National Academy of Medicine) in 2014. [11] [1]

Research in the Khavari laboratory focuses on genome regulation, signaling, noncoding RNAs, [12] and innovating new human tissue genetic models, with a special focus on the cutaneous epidermis. The lab accomplished the first genetic corrections of human skin tissue, [13] defined the minimal oncogenic gene set needed to transform normal human tissues into cancer, [14] and identified the kinetics of human malignant transformation using novel human tissue cancer models. [15] The Khavari group also identified new essential roles for a number of regulators in epidermal homeostasis, including ZNF750, MAF, MAFB, PRMT1, CSNK1A1, EHF, MPZL3, FDXR, TINCR, and ACTL6A. [16] It uncovered new regulators and effectors of Ras GTPases, including small noncoding snoRNAs as direct Ras-binders that modulate its function and mTORC2 as a new direct Ras downstream effector critical for the pro-proliferation impacts of Ras signaling. [17] The lab defined two major classes of genomic enhancers [18] in dynamic gene regulation and used multiomics and deep learning approaches to decode the combinatorial cis-regulatory DNA motif lexicon that drives epidermal differentiation. [19] The lab has innovated a number of technologies, including single cell perturb-ATAC-seq, [20] RNA protein interaction detection (RAPID), [21] RNA-protein microarray hybridization, [22] and mosaic human skin tissue models. [23] In cancer studies, the Khavari lab identified and characterized tumor specific keratinocytes in cutaneous squamous cell cancer, [24] characterized a new tumor suppressor pathway, [25] and defined a new sunlight induced oncogene in skin cancer. [26]

Selected Honors and Awards

Khavari has received a number of honors and awards, including most recently the Stephan Rothman Memorial Award, the highest award given by the Society of Investigative Dermatology. [27]

2021             Stephen Rothman Memorial Award, Society for Investigative Dermatology [27]

2018             Kligman-Frost Leadership Award, Society for Investigative Dermatology

2016             Lila & Murray Gruber Cancer Research Award, American Academy of Dermatology [28]

2014             National Academy of Medicine [29]

2012             American Skin Association 25th Anniversary Lifetime Scientific Achievement Award [30]

2009             American Association of Physicians

2008             Tanioku Kihei Memorial Award, Japanese Society for Investigative Dermatology [31]

2004             Marion B. Sulzberger Memorial Award, American Academy of Dermatology [32]

2004             William Montagna Award, Society for Investigative Dermatology

1999             American Society for Clinical Investigation

1998             HHMI Junior Faculty Scholar Award, Stanford University [33]

1997             V.A. Young Investigator Award, V.A. Palo Alto Health Care System [34]

1996             U.S. Presidential Early Career Award for Scientists and Engineers

1995             Shannon Award, National Institutes of Health

Notable Trainees and their current Affiliation

Related Research Articles

<span class="mw-page-title-main">Keratinocyte</span> Primary type of cell found in the epidermis

Keratinocytes are the primary type of cell found in the epidermis, the outermost layer of the skin. In humans, they constitute 90% of epidermal skin cells. Basal cells in the basal layer of the skin are sometimes referred to as basal keratinocytes. Keratinocytes form a barrier against environmental damage by heat, UV radiation, water loss, pathogenic bacteria, fungi, parasites, and viruses. A number of structural proteins, enzymes, lipids, and antimicrobial peptides contribute to maintain the important barrier function of the skin. Keratinocytes differentiate from epidermal stem cells in the lower part of the epidermis and migrate towards the surface, finally becoming corneocytes and eventually be shed off, which happens every 40 to 56 days in humans.

<span class="mw-page-title-main">Itch</span> Sensation that causes desire or reflex to scratch

Itch is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both are unpleasant sensory experiences, their behavioral response patterns are different. Pain creates a withdrawal reflex, whereas itches leads to a scratch reflex.

<span class="mw-page-title-main">Epidermolysis bullosa</span> Rare medical conditions that result in easy blistering of the skin and mucous membranes

Epidermolysis bullosa (EB) is a group of rare medical conditions that result in easy blistering of the skin and mucous membranes. Blisters occur with minor trauma or friction and are painful. Its severity can range from mild to fatal. Inherited EB is a rare disease with a prevalence in the United States of 8.2 per million live births. Those with mild cases may not develop symptoms until they start to crawl or walk. Complications may include esophageal narrowing, squamous cell skin cancer, and the need for amputations.

<span class="mw-page-title-main">Epidermal growth factor receptor</span> Transmembrane protein

The epidermal growth factor receptor is a transmembrane protein that is a receptor for members of the epidermal growth factor family of extracellular protein ligands.

<span class="mw-page-title-main">Amphiregulin</span> Protein-coding gene in the species Homo sapiens

Amphiregulin, also known as AREG, is a protein synthesized as a transmembrane glycoprotein with 252 aminoacids and it is encoded by the AREG gene. in humans.

<span class="mw-page-title-main">Hay–Wells syndrome</span> Medical condition

Hay–Wells syndrome is one of at least 150 known types of ectodermal dysplasia. These disorders affect tissues that arise from the ectodermal germ layer, such as skin, hair, and nails.

<span class="mw-page-title-main">Keratin 5</span>

Keratin 5, also known as KRT5, K5, or CK5, is a protein that is encoded in humans by the KRT5 gene. It dimerizes with keratin 14 and forms the intermediate filaments (IF) that make up the cytoskeleton of basal epithelial cells. This protein is involved in several diseases including epidermolysis bullosa simplex and breast and lung cancers.

<span class="mw-page-title-main">TP63</span> Protein-coding gene in the species Homo sapiens

Tumor protein p63, typically referred to as p63, also known as transformation-related protein 63 is a protein that in humans is encoded by the TP63 gene.

<span class="mw-page-title-main">Collagen, type VII, alpha 1</span> Protein found in humans

Collagen alpha-1(VII) chain is a protein that in humans is encoded by the COL7A1 gene. It is composed of a triple helical, collagenous domain flanked by two non-collagenous domains, and functions as an anchoring fibril between the dermal-epidermal junction in the basement membrane. Mutations in COL7A1 cause all types of dystrophic epidermolysis bullosa, and the exact mutations vary based on the specific type or subtype. It has been shown that interactions between the NC-1 domain of collagen VII and several other proteins, including laminin-5 and collagen IV, contribute greatly to the overall stability of the basement membrane.

<span class="mw-page-title-main">PTK6</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein kinase 6 is an enzyme that in humans is encoded by the PTK6 gene.

<span class="mw-page-title-main">FABP5</span> Protein-coding gene in the species Homo sapiens

Fatty acid-binding protein, epidermal is a protein that in humans is encoded by the FABP5 gene.

<span class="mw-page-title-main">KLK7</span> Protein-coding gene in the species Homo sapiens

Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the KLK7 gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE). It was later identified as the seventh member of the human kallikrein family, which includes fifteen homologous serine proteases located on chromosome 19 (19q13).

<span class="mw-page-title-main">ALOXE3</span> Protein-coding gene in the species Homo sapiens

Epidermis-type lipoxygenase 3 is a member of the lipoxygenase family of enzymes; in humans, it is encoded by the ALOXE3 gene. This gene is located on chromosome 17 at position 13.1 where it forms a cluster with two other lipoxygenases, ALOX12B and ALOX15B. Among the human lipoxygenases, ALOXE3 is most closely related in amino acid sequence to ALOX12B. ALOXE3, ALOX12B, and ALOX15B are often classified as epidermal lipoxygenases, in distinction to the other three human lipoxygenases, because they were initially defined as being highly or even exclusively expressed and functioning in skin. The epidermis-type lipoxygenases are now regarded as a distinct subclass within the multigene family of mammalian lipoxygenases with mouse Aloxe3 being the ortholog to human ALOXE3, mouse Alox12b being the ortholog to human ALOX12B, and mouse Alox8 being the ortholog to human ALOX15B [supplied by OMIM]. ALOX12B and ALOXE3 in humans, Alox12b and Aloxe3 in mice, and comparable orthologs in other in other species are proposed to act sequentially in a multistep metabolic pathway that forms products that are structurally critical for creating and maintaining the skin's water barrier function.

miR-203

In molecular biology miR-203 is a short non-coding RNA molecule. MicroRNAs function to regulate the expression levels of other genes by several mechanisms, such as translational repression and Argonaute-catalyzed messenger RNA cleavage. miR-203 has been identified as a skin-specific microRNA, and it forms an expression gradient that defines the boundary between proliferative epidermal basal progenitors and terminally differentiating suprabasal cells. It has also been found upregulated in psoriasis and differentially expressed in some types of cancer.

Paul S. Mischel is an American physician-scientist whose laboratory has made pioneering discoveries in the pathogenesis of human cancer. He is currently a Professor and Vice Chair of Research for the Department of Pathology and Institute Scholar of ChEM-H, Stanford University. Mischel was elected into the American Society for Clinical Investigation (ASCI), serving as ASCI president in 2010/11. He was inducted into the Association of American Physicians, and was elected as a fellow of the American Association for the Advancement of Science.

Cédric Blanpain is a Belgian researcher in the field of stem cells. He is a tenured professor of developmental biology and genetics at Université Libre de Bruxelles and director of the stem cell and cancer lab at its Faculty of Medicine. He was one of the first researchers in the world to use cell lineage tracing in cancer research and he showed for the first time the existence of cancer stem cells in solid tumors in vivo. He was selected by Nature as one of 10 People who mattered most in 2012 and he received the outstanding young investigator award of the International Society for Stem Cell Research.

Valentina Greco is an Italian-born biologist who teaches at the Yale School of Medicine as the Carolyn Walch Slayman Professor of Genetics and is an Associate Professor in the Cell Biology and Dermatology departments. Her research focuses on the role of skin stem cells in tissue regeneration.

Thomas S. Kupper is an American physician, academic, and clinician. His work with clinical and research experience spans dermatology, cutaneous oncology, and immunology. He is the Thomas B. Fitzpatrick Professor at Harvard Medical School, and chairs the Departments of Dermatology at Brigham and Women's Hospital. He also leads the Cutaneous Oncology Disease Center at the Dana Farber Cancer Institute.

Chromosome 1 open reading frame 68, or C1orf68, is a human gene which encodes for skin-specific protein 32. C1orf68 gene is expressed in the skin, is a part of the epidermal differentiation complex, and potentially plays a role in epidermal cornification, and epidermal barrier function.

CYLD cutaneous syndrome (CCS) is the recently designated term for three rare inherited cutaneous adnexal tumor syndromes: multiple familial trichoepithelioma (MFT1), Brooke–Spiegler syndrome (BSS), and familial cylindromatosis (FC). Cutaneous adnexal tumors are a large group of skin tumors that consist of tissues that have differentiated towards one of the four primary adnexal structures found in normal skin: hair follicles, sebaceous sweat glands, apocrine sweat glands, and eccrine sweat glands. CCS tumors are hair follicle tumors.

References

  1. 1 2 "Three faculty members elected to Institute of Medicine". Stanford.edu . Retrieved 2021-05-10.
  2. ↑ "Stanford University School of Medicine | SFB 829" . Retrieved 2021-05-10.
  3. ↑ Penn, Tiffany (October 30, 2014). "Paul Khavari, M.D. '88, Ph.D., HS '90, elected to Institute of Medicine". Yale School of Medicine . Yale.edu . Retrieved July 21, 2021.
  4. 1 2 "Med School appointments, promotions: 6/3/98". Stanford. Retrieved 2021-07-21.
  5. ↑ Conger, Krista (17 January 2010). "Paul Khavari appointed dermatology chair". Stanford.edu. Retrieved 2021-07-21.
  6. ↑ "Gerald Crabtree". SFARI . 2017-07-21. Retrieved 2021-05-10.
  7. 1 2 "Two young Stanford scientists receive Presidential award (1/97)". Stanford. Retrieved 2021-07-21.
  8. ↑ Begley, Sharon (11 November 2005). "Nature's Many Quirks Limit the Possibilities Of DNA-Based Drugs" . Wall Street Journal. ProQuest   398992336.
  9. ↑ "Stanford University School of Medicine | SFB 829" . Retrieved 2021-07-21.
  10. ↑ Conger, Krista (17 January 2010). "Paul Khavari appointed dermatology chair". med.stanford.edu (in Samoan). Retrieved 2021-05-10.
  11. ↑ "Institute of Medicine Elects 70 New Members, 10 Foreign Associates". www8.nationalacademies.org. Retrieved 2021-05-10.
  12. ↑ Lee, Carolyn S.; Mah, Angela; Aros, Cody J.; Lopez-Pajares, Vanessa; Bhaduri, Aparna; Webster, Dan E.; Kretz, Markus; Khavari, Paul A. (June 2018). "Cancer-Associated Long Noncoding RNA SMRT-2 Controls Epidermal Differentiation". Journal of Investigative Dermatology. 138 (6): 1445–1449. doi:10.1016/j.jid.2018.01.003. PMC   6814294 . PMID   29360484.[ non-primary source needed ]
  13. ↑ Choate, Keith A.; Medalie, Dan A.; Morgan, Jeff R.; Khavari, Paul A. (November 1996). "Corrective gene transfer in the human skin disorder lamellar ichthyosis". Nature Medicine. 2 (11): 1263–1267. doi:10.1038/nm1196-1263. PMID   8898758. S2CID   22281798.[ non-primary source needed ]
  14. ↑ Bolotin, Diana; Fuchs, Elaine (February 2003). "More than skin deep". Nature. 421 (6923): 594–595. doi: 10.1038/421594a . PMID   12571582. S2CID   4424529.
  15. ↑ Stuart, Darrin D; Sellers, William R (May 2013). "Targeting RAF-MEK-ERK kinase-scaffold interactions in cancer". Nature Medicine. 19 (5): 538–540. doi: 10.1038/nm.3195 . PMID   23652103. S2CID   6492513.
  16. ↑ Boxer, Lisa D.; Barajas, Brook; Tao, Shiying; Zhang, Jiajing; Khavari, Paul A. (15 September 2014). "ZNF750 interacts with KLF4 and RCOR1, KDM1A, and CTBP1/2 chromatin regulators to repress epidermal progenitor genes and induce differentiation genes". Genes & Development. 28 (18): 2013–2026. doi:10.1101/gad.246579.114. PMC   4173152 . PMID   25228645.[ non-primary source needed ]
  17. ↑ Kovalski, Joanna R.; Bhaduri, Aparna; Zehnder, Ashley M.; Neela, Poornima H.; Che, Yonglu; Wozniak, Glenn G.; Khavari, Paul A. (February 2019). "The Functional Proximal Proteome of Oncogenic Ras Includes mTORC2". Molecular Cell. 73 (4): 830–844.e12. doi:10.1016/j.molcel.2018.12.001. PMC   6386588 . PMID   30639242.[ non-primary source needed ]
  18. ↑ Conger, Krista (2017-08-15). "Genome architecture guides stem cell fate, Stanford researchers find". Scope. Retrieved 2021-05-10.
  19. ↑ Kim, Daniel S.; Risca, Viviana I.; Reynolds, David L.; Chappell, James; Rubin, Adam J.; Jung, Namyoung; Donohue, Laura K. H.; Lopez-Pajares, Vanessa; Kathiria, Arwa; Shi, Minyi; Zhao, Zhixin; Deep, Harsh; Sharmin, Mahfuza; Rao, Deepti; Lin, Shin; Chang, Howard Y.; Snyder, Michael P.; Greenleaf, William J.; Kundaje, Anshul; Khavari, Paul A. (November 2021). "The dynamic, combinatorial cis-regulatory lexicon of epidermal differentiation". Nature Genetics. 53 (11): 1564–1576. doi:10.1038/s41588-021-00947-3. PMC   8763320 . PMID   34650237. S2CID   238990464.[ non-primary source needed ]
  20. ↑ Rubin, Adam J.; Parker, Kevin R.; Satpathy, Ansuman T.; Qi, Yanyan; Wu, Beijing; Ong, Alvin J.; Mumbach, Maxwell R.; Ji, Andrew L.; Kim, Daniel S.; Cho, Seung Woo; Zarnegar, Brian J.; Greenleaf, William J.; Chang, Howard Y.; Khavari, Paul A. (January 2019). "Coupled Single-Cell CRISPR Screening and Epigenomic Profiling Reveals Causal Gene Regulatory Networks". Cell. 176 (1–2): 361–376.e17. doi:10.1016/j.cell.2018.11.022. PMC   6329648 . PMID   30580963.[ non-primary source needed ]
  21. ↑ Ramanathan, Muthukumar; Porter, Douglas F.; Khavari, Paul A. (March 2019). "Methods to study RNA–protein interactions". Nature Methods. 16 (3): 225–234. doi:10.1038/s41592-019-0330-1. PMC   6692137 . PMID   30804549.[ non-primary source needed ]
  22. ↑ Kretz, Markus; Siprashvili, Zurab; Chu, Ci; Webster, Dan E.; Zehnder, Ashley; Qu, Kun; Lee, Carolyn S.; Flockhart, Ross J.; Groff, Abigail F.; Chow, Jennifer; Johnston, Danielle; Kim, Grace E.; Spitale, Robert C.; Flynn, Ryan A.; Zheng, Grace X. Y.; Aiyer, Subhadra; Raj, Arjun; Rinn, John L.; Chang, Howard Y.; Khavari, Paul A. (January 2013). "Control of somatic tissue differentiation by the long non-coding RNA TINCR". Nature. 493 (7431): 231–235. Bibcode:2013Natur.493..231K. doi:10.1038/nature11661. PMC   3674581 . PMID   23201690.[ non-primary source needed ]
  23. ↑ Sen, George L.; Reuter, Jason A.; Webster, Daniel E.; Zhu, Lilly; Khavari, Paul A. (28 January 2010). "DNMT1 maintains progenitor function in self-renewing somatic tissue". Nature. 463 (7280): 563–567. Bibcode:2010Natur.463..563S. doi:10.1038/nature08683. PMC   3050546 . PMID   20081831.[ non-primary source needed ]
  24. ↑ Ji, Andrew L.; Rubin, Adam J.; Thrane, Kim; Jiang, Sizun; Reynolds, David L.; Meyers, Robin M.; Guo, Margaret G.; George, Benson M.; Mollbrink, Annelie; Bergenstråhle, Joseph; Larsson, Ludvig; Bai, Yunhao; Zhu, Bokai; Bhaduri, Aparna; Meyers, Jordan M.; Rovira-Clavé, Xavier; Hollmig, S. Tyler; Aasi, Sumaira Z.; Nolan, Garry P.; Lundeberg, Joakim; Khavari, Paul A. (September 2020). "Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma". Cell. 182 (6): 1661–1662. doi:10.1016/j.cell.2020.08.043. PMC   7505493 . PMID   32946785.[ non-primary source needed ]
  25. ↑ Ungewickell, Alexander; Bhaduri, Aparna; Rios, Eon; Reuter, Jason; Lee, Carolyn S; Mah, Angela; Zehnder, Ashley; Ohgami, Robert; Kulkarni, Shashikant; Armstrong, Randall; Weng, Wen-Kai; Gratzinger, Dita; Tavallaee, Mahkam; Rook, Alain; Snyder, Michael; Kim, Youn; Khavari, Paul A (September 2015). "Genomic analysis of mycosis fungoides and Sézary syndrome identifies recurrent alterations in TNFR2". Nature Genetics. 47 (9): 1056–1060. doi:10.1038/ng.3370. PMC   6091217 . PMID   26258847.[ non-primary source needed ]
  26. ↑ Lee, Carolyn S; Bhaduri, Aparna; Mah, Angela; Johnson, Whitney L; Ungewickell, Alexander; Aros, Cody J; Nguyen, Christie B; Rios, Eon J; Siprashvili, Zurab; Straight, Aaron; Kim, Jinah; Aasi, Sumaira Z; Khavari, Paul A (October 2014). "Recurrent point mutations in the kinetochore gene KNSTRN in cutaneous squamous cell carcinoma". Nature Genetics. 46 (10): 1060–1062. doi:10.1038/ng.3091. PMC   4324615 . PMID   25194279.[ non-primary source needed ]
  27. 1 2 "Paul Khavari, MD/PhD | 2021 SID Virtual Meeting | 2021 SID Awardees". SID Annual Meeting. Retrieved 2021-05-10.
  28. ↑ "Lila and Murray Gruber Memorial Cancer Research Award and Lectureship". www.aad.org. Retrieved 2021-10-18.
  29. ↑ "Three faculty members elected to Institute of Medicine". News Center (in Samoan). Retrieved 2021-10-18.
  30. ↑ "American Skin Association (ASA) Celebrates 25th Anniversary". American Skin Association (Press release). Retrieved 2021-10-18.
  31. ↑ "Tanioku Kihei Memorial Award - The Japanese Society for Investigative Dermatology". www.jsid.org. Retrieved 2021-10-18.
  32. ↑ П.М. Мазуркин (2013). ДИНАМИКА АЛЬФА-АКТИВНОСТИ ОБРАЗЦА 239PU В РАЗЛИЧНЫХ ШКАЛАХ ВРЕМЕНИ. Science and World. 2 (2). doi: 10.18411/a-2017-023 .
  33. ↑ "Med School appointments, promotions: 6/3/98". Stanford. Retrieved 2021-10-18.
  34. ↑ "Two young Stanford scientists receive Presidential award (1/97)". Stanford. Retrieved 2021-10-18.
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