PROGRAM FOR CLINICAL RESEARCH IN DERMATOLOGY

In September 2021, Dr. Yolanda Helfrich stepped down as Director of the Program for Clinical Research in Dermatology (PCRiD) after more than 10 years leading our department’s clinical research activities. In this role, she served as a primary investigator on multiple sponsored clinical trials and collaborated on translational research projects with other researchers within our department. In addition, she supervised faculty and residents serving as sub-investigators within the program and provided research mentorship to residents and medical students pursuing clinical research training in dermatology. As a member of the University of Michigan Research Board of Directors Clinical Trials Subcommittee, Dr. Helfrich helped implement the Clinical Trials Support Unit (CTSU) model at Michigan Medicine. She also served as one of the three inaugural medical directors for the Neurosciences and Sensory CTSU, which merged the research enterprises of Dermatology, Neurology, Neurosurgery, and Otolaryngology. Dr. Helfrich will continue to participate in clinical research within the department, serving as a senior faculty mentor and advisor to junior faculty, residents and medical students.

Newly appointed as PCRiD Director, Dr. Mio Nakamura obtained her M.S. in Clinical Research Design and Statistical Analysis from the University of Michigan School of Public Health and completed a two-year post-doctoral fellowship focused on psoriasis and clinical research at UCSF Dermatology. Although new to her role as its director, Dr. Nakamura is familiar with PCRiD from during her residency training and her prior work as a study coordinator while completing her graduate studies at Michigan. Dr. Nakamura will be leading efforts to expand clinical research activity, including establishing a new clinical research fellowship in our department.

BY THE NUMBERS

PCRiD Main Objectives

Yolanda Helfrich, MD Clinical Associate Professor Director, PCRiD (2011-2021)

Mio Nakamura, MD Clinical Assistant Professor Director, PCRiD

• To enhance patient care by providing opportunities for patients seeking new treatments

• To contribute to medical discovery by conducting clinical and translational studies to better understand dermatologic conditions and treatments

• To foster and train leaders in clinical and translational research

Areas of Study

• Plaque psoriasis

• Pustular psoriasis

• Atopic dermatitis

• Prurigo nodularis

• Cutaneous lupus

Aging Skin and Photobiology of Skin | Fisher Lab

Our Skin Aging and Photobiology research team seeks to understand the molecular and cellular mechanisms that drive the aging process in human skin. Our goal is to gain fundamental knowledge regarding the pathogenesis of age-related diseases resulting from deleterious alterations of the dermal extracellular matrix microenvironment. We use novel mouse models to investigate new concepts of aging and are particularly interested in studying the interplay between the extracellular microenvironment and decline of cell function during the aging process.

In addition, our group is investigating the novel hypothesis that age-related changes in the dermal compartment drive skin cancer initiation. Additional translational research studies are examining the clinical and molecular characteristics of skin aging, mechanisms of connective tissue remodeling in human skin, and mechanisms of interventions for aging and photoaged skin.

Publication Spotlight

Age-Related Elevation of HGF is Driven by the Reduction of Fibroblast Size in a YAP/ TAZ/CCN2 Axis-Dependent Manner. Xiang Y, Qin Z, Yang Y, Fisher GJ, Quan T.J Dermatol Sci. 2021 Apr;102(1):36-46.PMID: 33648801

Alterations in Extracellular Matrix Composition During Aging and Photoaging of the Skin. McCabe MC, Hill RC, Calderone K, Cui Y, Yan Y, Quan T, Fisher GJ, Hansen KC.Matrix Biol Plus. 2020 Jun 17;8:100041. PMID: 33543036 Free PMC article.

Rejuvenation of Aged Human Skin by Injection of Cross-linked Hyaluronic Acid. Cui Y, Wang F, Voorhees JJ, Fisher GJ.Plast Reconstr Surg. 2021 Jan 1;147(1S-2):43S-49S.

PMID: 33347074

Dermal Fibroblast CCN1 Expression in Mice Recapitulates Human Skin Dermal Aging

Quan T, Xiang Y, Liu Y, Qin Z, Yang Y, Bou-Gharios G, Voorhees JJ, Dlugosz AA, Fisher GJ. J Invest Dermatol. 2021 Apr;141(4S):1007-1016. PMID: 32800875

Lab Members

Gary Fisher – Harry Helfman Professor of Molecular Dermatology

Tianyuan He* – Assistant Research Scientist

Taihao Quan – Research Professor/Co-PI

Ken Calderone – Research Lab Technician

Yilei Cui – Research Lab Specialist

Chunfang Guo* – Research Lab Technician

Alex Ermilov – Research Lab Specialist

Joel Maust – Technical Writer

*Denotes lab member who departed

Autoimmunity/Immunogenetics in Skin | Gudjonsson Lab

The Skin Autoimmunity/Immunogenetics research group is investigating the immunological, genetic, and transcriptomic aspects of skin inflammatory and autoimmune diseases. Utilizing innovative bioinformatics, transcriptomic, and proteomic approaches, we have generated new insights into the nature of chronic autoimmune skin disorders, such as psoriasis, psoriatic arthritis, systemic lupus erythematosus and hidradenitis suppurativa.

A striking feature of autoimmune diseases is their increased prevalence in females, with an estimated 78% of those people affected with autoimmune diseases being women. Our group has identified the transcription factor VGLL3 as a master regulator of female-biased autoimmunity. Ongoing studies are focused on how VGLL3 mediates and promotes autoimmune responses, with the overall aim of developing novel preventive and therapeutic measures that may have major implications against a wide range of autoimmune diseases.

Publication Spotlight

Mechanisms of skin autoimmunity: Cellular and soluble immune components of the skin. Gudjonsson JE, Kabashima K, Eyerich K. J Allergy Clin Immunol. 2020 Jul;146(1):8-16. PMID: 32631499.

“Autoinflammatory psoriasis”-genetics and biology of pustular psoriasis. Uppala R, Tsoi LC, Harms PW, Wang B, Billi AC, Maverakis E, Michelle Kahlenberg J, Ward NL, Gudjonsson JE. Cell Mol Immunol. 2021 Feb;18(2):307-317. PMID: 32814870; PMCID: PMC8027616.

Contribution of plasma cells and B cells to hidradenitis suppurativa pathogenesis. Gudjonsson

JE, Tsoi LC, Ma F, Billi AC, van Straalen KR, Vossen ARJV, van der Zee HH, Harms PW, Wasikowski R, Yee CM, Rizvi SM, Xing X, Xing E, Plazyo O, Zeng C, Patrick MT, Lowe MM, Burney RE, Kozlow

JH, Cherry-Bukowiec JR, Jiang Y, Kirma J, Weidinger S, Cushing KC, Rosenblum MD, Berthier C, MacLeod AS, Voorhees JJ, Wen F, Kahlenberg JM, Maverakis E, Modlin RL, Prens EP. JCI Insight. 2020 Oct 2;5(19):e139930. PMID: 32853177; PMCID: PMC7566715.

Cytokinocytes: the diverse contribution of keratinocytes to immune responses in skin. Jiang Y, Tsoi LC, Billi AC, Ward NL, Harms PW, Zeng C, Maverakis E, Kahlenberg JM, Gudjonsson JE. JCI Insight. 2020 Oct 15;5(20):e142067. PMID: 33055429; PMCID: PMC7605526.

Psoriasis. Griffiths CEM, Armstrong AW, Gudjonsson JE, Barker JNWN. Lancet. 2021 Apr 3;397(10281):1301-1315. PMID: 33812489.

Lab Members

Johann Gudjonsson – Arthur C. Curtis Professor of Skin

Molecular Immunology

Allison Billi – Assistant Professor

Olesya Plazyo** – Research Investigator

Mrinal Sarkar – Assistant Research Scientist

Yutein (Andy) Chung** – Research Fellow

Chang Zeng* – Research Fellow

Craig Dobry – Research Lab Specialist

Mehrnaz Gharaee-Kermani – Research Lab Specialist

Austin Kidder – Lab Technician

Xianying Xing – Research Lab Specialist

Joseph Kirma – Student Trainee

Ranjitha Uppala – Student Trainee

Enze Xing – Student Trainee

*Denotes lab member who has departed **Denotes lab member who joined in FY22

Cutaneous Bioinformatics | Tsoi Lab

The Cutaneous Bioinformatics research group seeks to enhance the analysis and translation of experiments that study the genetics and genomics of different skin conditions. Our goal is to develop novel systems biology approaches and analysis pipeline for studies investigating the immunological mechanisms for different cutaneous diseases. Our research combines in silico discoveries and bench experiments to advance our understanding of genomics in autoimmune skin disorders. The Cutaneous Bioinformatics team works closely with other investigators and research teams within our department and at Michigan Medicine to advance research discovery.

Publication Spotlight

Causal relationship and shared genetic loci between psoriasis and type 2 diabetes through trans-disease meta-analysis. Patrick MT, Stuart PE, Zhang H, Zhao Q, Yin X, He K, Zhou XJ, Mehta NN, Voorhees JJ, Boehnke M, Gudjonsson JE, Nair RP, Handelman SK, Elder JT, Liu DJ, Tsoi LC#. J Invest Dermatol. 2020 Dec 29:S0022202X(20)32394-0. Epub ahead of print. PMID: 33385400.

Associations between COVID-19 and skin conditions identified through epidemiology and genomic studies. Patrick MT, Zhang H, Wasikowski R, Prens EP, Weidinger S, Gudjonsson JE, Elder JT, He K, Tsoi LC#. J Allergy Clin Immunol. 2021 Jan 21:S0091-6749(21)00084-1. PMID: 33485957; PMCID: PMC7825803.

Advancement in predicting interactions between drugs used to treat psoriasis and its comorbidities by integrating molecular and clinical resources. Patrick MT, Bardhi R, Raja K, He K, Tsoi LC#. J Am Med Inform Assoc. 2021 Jun 12;28(6):1159-1167. PMID: 33544847; PMCID: PMC8200269.

Cytokine responses in non-lesional psoriatic skin as clinical predictor to anti-TNF agents Tsoi LC#, Patrick MT, Shuai S, Sarkar MK, Chi S, Ruffino B, Billi AC, Xing X, Uppala R, Zang C, Fullmer J, He Z, Maverakis E, Mehta NN, Perez White BE, Getsios S, Helfrich Y, Voorhees JJ, Kahlenberg JM, Weidinger S, Gudjonsson JE. J Allergy Clin Immunol. 2021 Jul 31:S0091-6749(21)01144-1. PMID: 34343561.

Lab Members

Lam C. (Alex) Tsoi – Assistant Professor of Dermatology, Computational Medicine & Bioinformatics, and Biostatistics (SPH)

Matthew Patrick – Research Investigator

Sreeskandarajan Sutharzan* – Research Fellow

Rachael Wasikowski – Research Specialist Associate

Qinmengge Li – Student Trainee

Haihan Zhang – Student Trainee

*Denotes lab member who departed

Hair Follicle Morphogenesis, Wound Healing and Skin Cancer | Wong Lab

The Wong Lab studies how stem cells in the skin and hair follicle coordinate their behaviors to maintain barrier function, regenerate hair and heal wounds. These studies have important implications for patients who suffer from alopecia, acne, seborrheic dermatitis and ichthyosis.

In addition, our group has a long-standing interest in understanding the genetic factors that drive the formation of basal cell carcinoma (BCC), the most common cancer worldwide. We are particularly interested in studying the interplay between Hedgehog and Notch signaling, and how these two pathways work together to modulate tumorigenesis and drug response. As members of both the Departments of Dermatology, as well as Cell and Developmental Biology (CDB), we utilize basic and translational approaches to uncover novel insights into multiple aspects of skin biology.

Publication Spotlight

Preparing the Hair Follicle Canal for Hair Shaft Emergence. Mesler AL, Benedeck RE, Wong SY. Exp Dermatol. 30(4): 472-478, 2021. PM33025661/PMC8016696

Lab Members

Sunny Wong – Associate Professor of Dermatology, and Cell and Developmental Biology

Shih-Ying Tsai – Research Fellow

Rachel Benedeck* – Lab Technician Associate

Noah Ford – Lab Technician Associate

Natalia Veniaminova – Research Lab Specialist

Owen Doane* – Student Trainee

Adrien Hartigan – Student Trainee

Thomas Huyge – Student Trainee

Virginia Ju – Student Trainee

Kenneth G Trieu – Student Trainee

*Denotes lab member who departed

For additional lab information and research highlights, please visit www.skinlab1.com

Sunny Wong and members of his laboratory say farewell to Karen Myers and Rachel Benedeck. Karen retired from dermatology after over 20 years of service at the University of Michigan. Rachel is pursuing a graduate degree at the University of Michigan.

Psoriasis Genetics and Pathophysiology | Elder Lab

Our Psoriasis Genetics and Pathophysiology research group has a long-standing interest in genetic studies of psoriasis. This ongoing research utilizes the power of large genome-wide association studies, along with RNA-seq and ATAC-seq of blood-derived T-cell and dendritic cell subsets, and the largest collection of psoriasis genomic DNA samples in the world to enhance our mechanistic understanding of the genetic basis of psoriasis and psoriatic arthritis.

Our group also seeks to understand the pathogenic mechanisms that predispose patients with cutaneous psoriasis to develop psoriatic arthritis. The goal of this research is to identify biomarkers for the development of psoriatic arthritis in patients with cutaneous psoriasis and integrate those biomarkers to develop a clinically useful tool for psoriatic arthritis prediction.

Publication Spotlight

A High-Resolution HLA Reference Panel Capturing Global Population Diversity Enables Multi-Ethnic Fine-Mapping in HIV Host Response. Luo Y, Kanai M, Choi W, Li X, Yamamoto K, Ogawa K, GutierrezArcelus M, Gregersen PK, Stuart PE, Elder JT, Fellay J, Carrington M, Haas DW, Guo X, Palmer ND, Chen YI, Rotter JI, Taylor KD, Rich SS, Correa A, Wilson JG, Kathiresan S, Cho MH, Metspalu A, Esko T, Okada Y, Han B, NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, McLaren PJ, Raychaudhuri S. Nature Genetics. 53:1504-1516, 2021. PMID: 34611364

ALK3 is not Required for the Embryonic Development, Homeostasis and Repopulation of Epidermal Langerhans Cells in Steady and Inflammatory States. Yu Q, Parajuli N, Yi Q, Mishima Y, Elder JT, Zhou L, Mi Q-S. Journal of Investigative Dermatology. PMID: 33385400

Large-Scale Imputation of KIR Copy Number and HLA Alleles in North American and European Psoriasis Case-Control Cohorts Reveals Association of Inhibitory KIR2DL2 with Psoriasis. Ahn R, Vukcevic D, Motyers A, Nititham J, Squire D, Hollenbach JA, Norman PJ, Ellinghaus E, Nair RP, Tsoi LC, Oksenberg J, Foerster J, Lieb W, Weidinger S, Franke A, Elder JT, Jorgenson E, Leslie S, Liao W. Front Immunol. 2021 Jun 11; 12:684326. PMID: 34177931, PMCID PMC8231283.

Causal Relationship and Shared Genetic Loci Between Psoriasis and Type 2 Diabetes Through Trans-Disease Meta-Analysis. Patrick MT, Stuart PE, Zhang H, Zhao Q, Yin X; He K, Zhou XJ, Mehta NN, Voorhees JJ, Boehnke M, Gudjonsson JE, Nair RP, Handelman SK, Elder JT, Liu DJ, Tsoi LC. Journal of Investigative Dermatology. 2021 Jun; 141(6):1493-1502. PMID: 33385400; PMCID: PMC8154633.

Lab Members

James T. Elder – Kirk D. Wuepper Professor of Molecular Genetic Dermatology

Rajan Nair – Associate Research Scientist

Zhaolin Zhang – Research Fellow

Philip Stuart – Research Lab Associate

Directed by Dr. Elder, our long-standing NIH T32 Training Program supports post-doctoral research training in Cell and Molecular Dermatology.

Current and recent T32 fellows:

Yutein Chung** – Research Fellow

William Giblin, Jr.* – Research Fellow

Grace Hile (House Officer) – Research Fellow

Michael McFadden – Research Fellow

Elisabeth Pedersen** (House Officer) – Research Fellow

*Denotes lab member who has departed **Denotes lab member who joined in fiscal year 2022

Skin Cancer Biology | Dlugosz Lab

Our research team has a long-standing interest in understanding the molecular and cellular basis of non-melanoma skin cancer. This work is based heavily on the development and characterization of novel mouse models, complemented by analysis of human tissue samples and cell lines. Our current work addresses two types of non-melanoma skin cancer: basal cell carcinoma (BCC), the most common form of skin cancer; and Merkel cell carcinoma (MCC), a rare but highly aggressive form of skin cancer, linked in many cases to a viral infection.

Our BCC research centers upon defining the impact of aging on BCC tumorigenesis, examining crosstalk between BCC tumor cells and other cells in the tumor micro-environment, and investigating the basis of inter-tumor heterogeneity. Our MCC studies are focused on defining the MCC cell of origin, identifying the viral proteins that drive MCC development, elucidating transcription factors that contribute to MCC cell identity, and generating a robust mouse model for preclinical studies to ultimately improve treatment outcomes for patients with this deadly cancer. Our extensive expertise in mouse model development enables our laboratory to also contribute to studies on cancers arising in internal organs.

Publication Spotlight

Cancer-Associated Fibroblasts Promote Aggressive Gastric Cancer Phenotypes via Heat Shock Factor 1-Mediated Secretion of Extracellular Vesicles. Grunberg N, Pevsner-Fischer M, Goshen-Lago T, Diment J, Stein Y, Lavon H, Mayer S, Levi-Galibov O, Friedman G, OfirBirin Y, Syu LJ, Migliore C, Shimoni E, Stemmer SM, Brenner B, Dlugosz AA, Lyden D, RegevRudzki N, Ben-Aharon I, Scherz-Shouval R. Cancer Res. 2021 Apr 1;81(7):1639-1653.

PMID: 33547159; PMCID:PMC8337092.

Inhibition of Hedgehog Signaling Alters Fibroblast Composition in Pancreatic Cancer.

Steele NG, Biffi G, Kemp SB, Zhang Y, Drouillard D, Syu L, Hao Y, Oni TE, Brosnan E, Elyada

E, Doshi A, Hansma C, Espinoza C, Abbas A, The S, Irizarry-Negron V, Halbrook CJ, Franks NE, Hoffman MT, Brown K, Carpenter ES, Nwosu ZC, Johnson C, Lima F, Anderson MA, Park Y, Crawford HC, Lyssiotis CA, Frankel TL, Rao A, Bednar F, Dlugosz AA, Preall JB, Tuveson

DA, Allen BL, Pasca di Magliano M. Clin Cancer Res. 2021 Apr 1;27(7):2023-2037. PMID: 33495315; PMCID:PMC8026631.

Dermal Fibroblast CCN1 Expression in Mice Recapitulates Human Skin Dermal Aging

Quan T, Xiang Y, Liu Y, Qin Z, Yang Y, Bou-Gharios G, Voorhees JJ, Dlugosz AA, Fisher GJ. J Invest Dermatol. 2021 Apr;141(4S):1007-1016. PMID: 32800875; PMCID: PMC7881053.

Lab Members

Andrzej Dlugosz – Poth Professor of Cutaneous Oncology

Professor of Dermatology, and Cell and Developmental Biology

Marina Grachtchouk – Assistant Research Scientist

Li-Jyun Syu – Assistant Research Scientist

Monique Verhaegen – Research Assistant Professor/Co-PI

Elisabeth Pedersen** (House Officer) – Research Fellow

Dawn Wilbert – Lab Technician/Lab Manager

Jacob Arche – Lab Technician

Stefan Stoll – Research Lab Specialist Lead

Anissa Alam** – Student Trainee

Nihal Lingam** – Student Trainee

Shreya Mishra** – Student Trainee

Deepa Ramesh** – Student Trainee

John Runge* – Student Trainee

Emma Sortor** – Student Trainee

Julia Van Goor* – Student Trainee

Emily Walter** – Student Trainee

*Denotes lab member who departed **Denotes lab member who joined in fiscal year 2022