Dermatology Research Labs

Research Description

The current projects in Dr. Budunova’s lab are centered on the role of the glucocorticoid receptor (GR) as a tumor suppressor gene in skin. We showed that skin-specific GR transgenic animals are resistant to skin carcinogenesis and GR KO animals are more sensitive to skin tumor development.  We are also interested in the role of GR in the maintenance of skin stem cells (SC). We found that GR/glucocorticoids inhibit the expression of numerous SC markers in skin including CD34- a marker of hair follicular epithelial SC and reduce the proliferative potential of skin SCs.

The glucocorticoids remain among the most effective and frequently used anti-inflammatory drugs in dermatology. Unfortunately, patients chronically treated with topical glucocorticoids, develop side effects including cutaneous atrophy. GR controls gene expression via (i) transactivation that requires GR dimerization and binding as homo-dimer to gene promoters and (ii) transrepression that is chiefly mediated via negative interaction between GR and other transcription factors including pro-inflammatory factor NF-kB. In general, GR transrepression is the leading mechanism of glucocorticoid anti-inflammatory effects, while many adverse effects of glucocorticoids are driven by GR transactivation.

Our laboratory has been involved in delineation of mechanisms underlying side effects of glucocorticoids in skin. Using GRdim knockin mice characterized by impaired GR dimerization and activation, we found that GR transactivation plays an important role in skin atrophy. These data suggested that non-steroidal selective GR activators (SEGRA) that do not support GR dimerization, could preserve therapeutic potential of classical glucocorticoids but have reduced adverse effects in skin.  We are testing effects of the novel SEGRA called Compound A– a synthetic analog of natural aziridine precursor from African bush Salsola Botch in skin. We have also established anti-cancer GR-dependent activity of Compound A in epithelial and lymphoma cells.

Using knockout mice for the major GR target genes including Fkbp5 (GR chaperone) and DDIT4/REDD1 (one of the major negative regulators  of mTORC), we discovered that blockage of Fkbp5 and REDD1 significantly changes GR function and greatly protects skin against glucocorticoid-induced atrophy. This suggests a novel GR-targeted anti-inflammatory therapy where glucocorticoids are combined with inhibitors of GR target genes.

For more information, please see Dr. Budunova’s faculty profile.

Publications

See Dr. Budunova's publications in PubMed.

Contact

Contact the Budunova Lab at 312-503-4669 or visit in the Montgomery Ward Building, 303 E. Chicago Avenue, Ward 9-015, Chicago, IL 60611

Faculty: Irina Budunova, MD, PhD

Research Associates: Pankaj Bhalla, PhD, Gleb Baida, PhD, Anna Klopot, PhD

Research Description

We employ cutting-edge genomics approaches to identify the genetic basis of inherited and acquired immunological disorders and skin cancer.

As an example, we have recently identified the genes and mutations underlying cutaneous T cell lymphoma, an incurable non-Hodgkin lymphoma of skin-homing T cells. The genes are components of the DNA damage, chromatin modifying, NF-kB and the T cell receptor signaling pathways. We are currently employing a comprehensive approach using human tissues and animal models to investigate the functions of these genes. We are confident these studies will allow us to elucidate the pathophysiology of this cancer and lead to the identification of novel therapeutic targets.

Work in the lab is funded by National Cancer Institute, Dermatology Foundation, American Skin Association and American Cancer Society. For further information, please also see Dr. Choi's faculty profile.

Publications

See Dr. Choi's publications on PubMed.

Contact

Contact Dr. Choi.

Research Description

The Lavker/Peng laboratory focuses on the biology of epithelial stem cells and the roles of microRNAs (miRNAs) in regulating epithelial homeostasis. Initial investigations on microRNAs (miRNAs) focused on corneal epithelial-preferred miRNAs. Specifically, miR-205 undergoes a unique form of regulation through an interaction with the corneal-preferred miR-184 to maintain SHIP2 levels. SHIP2, a lipid phosphatase, is a target of miR-205, which enhances keratinocyte survival through PI3K-Akt signaling. This miRNA also positively regulates keratinocyte migration by altering F-actin organization and decreasing cell-substrate adhesion. The lab has also focused on miR-31, which targets factor inhibiting hypoxia-inducible factor-1 (FIH-1). FIH-1 impairs epithelial differentiation via attenuation of Notch signaling. Our results define a previously unknown mechanism for keratinocyte fate decisions where Notch signaling potential is, in part, controlled through a miR-31/FIH-1 nexus. This provides a rationale for development of treatment regimens in patients with diseases affecting abnormal epithelial differentiation (e.g., psoriasis) using inhibitors of FIH-1.

The laboratory has also been interested in the roles of autophagy in stratified epithelia. We were the first to use single cell RNA sequencing assay and established a comprehensive atlas of genes of the anterior segmental epithelia from wild-type and autophagy-deficient mice. In addition, we showed how ciliogenesis and autophagy are coordinately regulated in the corneal epithelium. Furthermore, we have demonstrated that depletion of miRs-103/107 in vitro and in vivo resulted in an inhibition of autophagy at the end stage and that PLD1/PKC/dynamin1 pathway plays a critical role in regulation of end-stage autophagy. This was the first demonstration of how end-stage autophagy is regulated in stratified epithelia. We have also reported that autophagy has a positive role in proliferative capacity of the limbal epithelium. Our laboratory has demonstrated that autophagy plays protective roles against a variety of stress (e.g., nitrogen mustard-induced corneal injury) in the cornea.

Our group is actively engaged in conducting research in skin and corneal inflammation. We demonstrated that enhancement of autophagy activates myeloid anti-inflammatory M2 macrophages in mouse skin. We also demonstrated that ACE2 deficiency resulted in a cytokine storm-driven corneal inflammation. We examined the efficacy of a novel synthetic high-density lipoprotein nanoparticle (HDL NPs)-based eye drop in alleviating corneal inflammation. HDL NP can also delivery functional microRNAs (e.g., miR-205) into corneal epithelial cells.

Publications

For publication information and more, see the Lab faculty’s profiles:

Robert Lavker, PhD, Han Peng, PhD

Contact Lavker/Peng Lab

Contact the Lavker/Peng Lab at 312-503-2043 or visit us on campus in the Montgomery Ward Building, 303 E. Chicago Avenue, Ward 9-120, Chicago, Illinois, 60611.

Faculty

Robert M. Lavker, PhD, Han Peng, PhD

Postdoctoral Fellows

Elwin Dean Clutter II, Ph.D.

Elif Kayaalp Nalbant, Ph.D.

Seyedeh Parisa Foroozandehasl, Ph.D.

Technician

Wending Yang, PhD

Research Description

​The lab has a significant interest in elucidating how various drug compounds direct macrophage differentiation towards either an M1 classically activated vs. M2 alternatively activated phenotype, the latter being vital in tissue repair. The team has developed methods for repurposing drugs, such as the use of ultra-high doses of vitamin D3 in controlling innate immune activation in the skin. Recent discoveries from the lab demonstrate that vitamin D upregulates macrophage autophagy which is critical for the development of tissue repair M2 macrophages in the skin. The methodologies used in the lab spread the gamut from cell biology, to model organisms, to clinical trials.  ​The goal of the lab is to ultimately translate findings into the development of therapeutics for mediating skin and wound repair. This work has led to national and international recognition for the potential use of vitamin D3 and other immune-modifying drugs following skin injury in clinical scenarios such as UV sunburns and skin wounds from toxic chemical exposure.

Publications

For publication information and more, see Kurt Lu, MD.

Contact

Contact the Lu Lab at 312-503-4075 or visit in the Montgomery Ward Building, 303 E. Chicago Avenue, Ward 4-202, Chicago, IL 60611

Faculty: Kurt Lu, MD

Research Associates: Venus Onay, PhD; Dauren Biyashev, PhD

Research Technologists: Spencer Evans; Michael Demczuk

The Paller laboratory primarily focuses on inflammatory skin diseases and the development of novel therapeutic approaches. The laboratory has studied diabetic wounds for the past decade and is now focused on understanding the role of various subtypes of NaV1.8⁺ sensory nerves with cutaneous afferents in healing. The laboratory uses genetic modulation of specific nerve subsets (labeled, DTX-depleted, DREADD alterations) in mouse models to evaluate not just the impact on wound healing, but also in a variety of mouse models of inflammatory skin diseases in which cutaneous innervation is altered. As an extension of this work, the Paller laboratory is investigating the underlying molecular basis for itch and pain in skin disease and how sensory nerve subsets may contribute. Some of these studies with mice mesh with Dr. Paller’s ongoing clinical research on the same disorders in humans.

A second area of interest is the role of obesity in altering immune responses in inflammatory skin disorders such as psoriasis. In both humans and mouse models, obesity increases the severity of psoriasis. The Paller laboratory has shown that the pro-inflammatory effect of obesity depends on reduction of adiponectin and that adiponectin mimetics reverse the tending towards psoriasis exacerbation through suppression of PPAR-gamma activation, reduction of Th17 skewing and increases in Treg cell activity.

Dr. Paller’s clinical interest includes rare genetic disorders of skin – and Northwestern hosts center of excellence for ichthyosis and epidermolysis bullosa. Through this connection and with the Northwestern Skin Biology and Diseases Resource-based Center, Northwestern has an extensive biobank of cultured skin cells, tissue, and tape stripped skin from patients with these genetic disorders. The laboratory has participated in assessment of the genetically-altered skin using omics approaches, including lipidomics.

We are actively investigating the role of ceramides, crucial components of the skin's lipid barrier, in maintaining skin integrity especially in inflammatory skin diseases such as atopic dermatitis (AD), psoriasis, and ichthyosis. In conditions like AD, there is a known deficiency in ceramides, contributing to the impaired barrier function observed in the disease. Similarly, in ichthyosis and psoriasis, alterations in ceramide levels and composition are associated with disruptions in the skin barrier. Although not achieved to date, replenishment of deficient ceramides is a focus in therapeutic strategies for these inflammatory skin conditions, emphasizing their importance in restoring and fortifying the skin barrier to alleviate symptoms and enhance overall skin health. Explorations of epidermal barrier lipids have used targeted lipidomics, which specifically analyze known lipid sets. To comprehensively understand the lipidomic changes in these skin diseases, an unbiased lipidomic analysis is essential. Similar to the unbiased generation of large datasets have been used to explore changes in gene and protein expression patterns in disease, we are utilizing untargeted lipidomics as an unbiased approach to discovering new lipids in healthy or diseased skin samples to gain insights into the broader lipid landscape.

Research in nanotechnology began more than 15 years ago with the demonstration that spherical nucleic acids (SNAs; developed in the Mirkin laboratory in Chemistry) have the unique property of penetrating intact human skin, thus able to deliver oligomers to suppress gene targets in both the epidermis and dermis. Genes of interest relevant to diabetes (GM3S), psoriasis (TGFA, IL17R), and scars (TGFB, CTGF) have been successfully targeted in models.

Publications

For publication information and more, see Amy Paller's, MS/MD faculty profile.

Contact Paller Lab

Contact the Paller Lab at 312-503-0298 or visit us on campus in the Montgomery Ward Building at 303 E. Chicago Avenue, Ward 9-070, Chicago, Illinois, 60611.

Faculty:

Amy S. Paller, MD/MS

Senior Research Associate/Lab manager:

Nihal Kaplan, PhD (n-kaplan@northwestern.edu)

Postdoctoral Scholar:

Lisa Maccio-Maretto (lisa.macciomaretto@northwestern.edu)

Research Technologist:

Jackie Crystal Wang (jackie.wang@northwestern.edu)

Pre-doctoral fellows:

Lynna Juliann Yang (lynna.yang@northwestern.edu)

Madeline Claire Scoles (madeline.scoles@northwestern.edu)

Medical Students:

Natalie Bourand (natalie.bourand@northwestern.edu)

Simrita Deol (simrita.deol@northwestern.edu)

Keana M. Khodadad (keana.khodadad@northwestern.edu)

Eleanor Bethany Ostroff (eleanor.ostroff@northwestern.edu)

Hannah Soltani (hannah.soltani@northwestern.edu)

Graduate/Undergraduate/Highschool student members:

Emmy Lev, Janie Zhengyi Lin, Andrea Liu, Mikaella Moraga, Mason Olivarez, Jordan Aisling Raizer, Malak Saad, Winnie Sung, Danielle Grace Toleno, and Kyle Wilson.

The Troyanovsky lab’s research focuses on cadherin, intercellular adhesion and signaling. Classic cadherins are critical proteins mediating cell-cell adhesion and various signaling pathways responsible for cellular proliferation, differentiation and morphogenesis.  Abnormalities in this system are causal factors in many pathologies, including cancer. The molecular mechanisms of cadherin-based adhesion, however, are largely unknown. How do cadherins establish the adhesion contact? How do they interact with the cytoskeleton? What are the signaling pathways they control? Our laboratory's work is centered around these questions. We are currently working on the following specific projects:

• An individual cadherin molecule’s adhesion site is very weak. To mediate tight adhesion, cadherin molecules form clusters. Recently our lab showed that cadherin clustering is based on two different mechanisms. First, using an extracellular cis-binding site, cadherin sticks laterally in small groups. Additional clustering is promoted by the actin cytoskeleton, binding to which limits cadherin diffusion. The aim of our current study is to understand the regulation of cadherin clustering through modulation of the cadherin-actin filament coupling.
• The formation of cadherin adhesive clusters interconnected to the cytoskeleton is not sufficient to establish functional intercellular junctions. The junctions stimulate formation of actin bundles that is required for epithelial cells to organize their actin cytoskeleton. How adherens junctions initiate actin bundle formation is another direction in our research.
• Cadherin is not the only transmembrane protein in adherens junctions. These structures contain adhesion proteins from the nectin family as well as numerous signaling proteins. We showed that one of such proteins, gamma-secretase, interacts with E-cadherin through p120-catenin. The roles of nectins and gamma-secretase and the ways they are recruited into adherens junctions are also areas of focus in our lab.

For more information see Sergey Troyanovsky’s, PhD, faculty profile.

Publications

View Dr. Troyanovsky's publications at PubMed.

Contact

Email Dr. Troyanovsky

Phone the Troyanovsky Lab at 312-503-9275

Lab Staff

Research Associates

Regina Troyanovsky, PhD, Indrajyoti Indra, PhD

Postdoctoral Fellows

Mohammad Abu-Laban, PhD

Research Description

The Perez White laboratory strives to conduct leading-edge research in the field of epidermal biology with the ultimate goal of impacting medicine and advancing our understanding of skin. To this end, we incorporate hypothesis-driven research with innovative disease models and discovery approaches. Specifically, we employ three-dimensional models of bioengineered reconstituted human epidermis and mouse models with proteomics, RNA-sequencing, or microarray analysis. We uniquely exploit our use of primary human cells to identify key signal transduction mechanisms that drive the physiological state and how these pathways may be hijacked to contribute to pathological states.

The overall aim of our research direction is to define Eph receptor tyrosine kinase signal networks underlying epidermal homeostasis. As little is known about Eph receptors in skin biology, we performed a proteomics screen to generate a directory of EphA2-interacting proteins in primary human epidermal keratinocytes. So far, this rich resource has led us to appreciate an unrecognized role for EphA2 in tight junction morphogenesis. EphA2 promotes the de novo assembly and functional integrity of the epidermal tight junction barrier. The tight junction barrier is an indispensable structural network that prevents the movement of small molecules (water, solutes, ions, proteins, and pathogens, infectious agents, and allergens) into or out of an organism. Perturbations in tight junctions are relevant to several skin disorders such as cancer, atopic dermatitis, and psoriasis.

For more information, please see Dr. Perez White’s faculty profile.

Publications

See Dr. Perez White's publications in PubMed.

Contact

Contact the Perez White Lab at 312-503-5452 or visit us on campus in the Montgomery Ward Building, 303 E. Chicago Avenue, Ward 9-321, Chicago, IL 60611.

Faculty: Bethany Perez White, PhD

Research Faculty: Bo Shi, PhD