Her NIH-funded basic science and clinical research — which ranges from immune-mediated inflammatory diseases in children to diabetic wound healing and topical gene therapy for skin disorders — is frequently published in top journals, including JAMA, The New England Journal of Medicine, The Journal of Clinical Investigation and Proceedings of the National Academy of Sciences.
Paller, a faculty member since 1988, also serves as director of the Northwestern University Skin Disease Research Center (SDRC), one of six SDRCs in the country.
“I am so lucky to have a career that encourages collaborative activities, focuses on training the next generation, and transitions research success towards better care of my patients,” says Paller, also a professor of Pediatrics and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
What are your research interests?
My laboratory has worked for the last few decades on the role of membrane-based glycosphingolipids in signaling in the epidermis. Most recently, our work has focused on the role of ganglioside GM3 in diabetes, especially in suppressing growth factor receptor signaling. We are also probing the role of obesity and diabetes in exacerbating inflammatory skin disease and, in joint studies with Dr. Daniela Menichella and Dr. Richard Miller, are evaluating the molecular basis for nerve retraction and regeneration, and how it is altered in diabetes.
In collaborative studies with Dr. Chad Mirkin, we have leveraged spherical nucleic acids (SNAs) — nanoconstructs of spherically arrayed siRNA or DNA — for topically-applied gene suppression. We have used these SNAs to down-regulate mRNA expression of GM3 synthase, as a therapeutic tool to reverse impaired diabetic wound healing. We have also used topically applied SNA gene regulation to target the increased cytokine expression in psoriasis and growth factor overexpression in scars.
In the clinical arena, my investigator-initiated research is focused largely on immune-mediated and genetic inflammatory skin diseases. I have been working with collaborators to define the underlying immunophenotype of children with eczema/atopic dermatitis (AD) and of patients with the ichthyoses, a group of genetic disorders characterized by poor epidermal barrier, inflammation and scaling.
Our clinical research unit in dermatology is the largest in the country, and I direct the pediatric dermatology component. In addition to being a lead site for several trials of first-in-kind medications, we also are developing new ways to document disease severity and patient-reported outcomes. I am working with Dr. Richard Gershon and Dr. David Cella in testing PROMIS (Patient-Reported Outcomes Measurement Instrument Systems) instruments in children with AD. We are also working with Dr. John Rogers’ group in applying his skin sensor devices.
What is the ultimate goal of your research?
As with any physician-scientist, my interest is to discover what drives disease (of the skin) and whether we can integrate that new knowledge towards intervention. My clinical interests have long been genetic skin disorders and inflammatory skin diseases in children. As a result, I see firsthand the huge unmet need for improved diagnostics and therapy — and have the patient population to test discoveries. During the past 30 years of working at Northwestern, I have had the good fortune of taking many discoveries from bench to bedside, either from my lab or often through collaborative discoveries.
Which honors are you most proud of and why?
I have been fortunate to receive many honors in my career from major organizations, most recently the Livingood Award from the American Academy of Dermatology, the Kung-Sun Oh Memorial Medal from Yonsei University, and the prestigious Stephen Rothman Award from the Society for Investigative Dermatology.
But the recent honor I am most proud of was receiving the Paula Stern Outstanding Women in Science and Medicine Award from Northwestern. As faculty, we are recognized nationally and internationally for our accomplishments and service, but to be honored by peers whom we cherish here at Northwestern (my home for almost 40 years) is priceless. This honor recognized both my research activities and also the difference I made in moving forward the careers of trainees and younger faculty. I am passionate about the discoveries — especially those that have translated into helping my patients — but most important will be the legacy I leave in exciting young people to be superb physicians, excellent investigators, and leaders who make a difference in our world.
What do you enjoy about teaching/mentoring young scientists in the lab?
My greatest pleasure is to watch young people gain knowledge, get excited about concepts and discoveries, and advance their own careers. I have had the pleasure of being both residency and fellowship director, and of mentoring hundreds of students, residents, fellows and junior faculty. Some have gone on to become chairs, leaders of laboratories, and heads of their own specialty programs; most are in academics. I am sure that I learn as much, if not more, from my colleagues and trainees as I could possibly impart to them. Together, we reinforce our passion for science — and only together are we able to make discoveries that have an impact.
Who makes up your research team and what role does each individual play in your research?
I have two wonderful research teams — one in the laboratory and one in the clinic.
In the bench laboratory arena, I wear two hats: one as director of my own lab and the other as PI for the NIH P30-funded Skin Disease Research Center (SDRC). The SDRC has more than 70 members from 14 different departments at the institution. Our service cores span three major areas to support Northwestern faculty: Dr. Bethany Perez-White leads the Skin Tissue Engineering Core, which generates human skin equivalents for investigators, and she is ably supported by co-director Dr. Kathleen Green and our research technologist Paul Hoover. The Morphology and Phenotyping Core, led by Dr. Joan Guitart and Dr. Robert Lavker, primarily does histological analysis of skin specimens, including mouse skin. With the assistance of research technologist Aya Kobeissi, we are developing new histologic techniques, such as tyramide-based multi-color staining. This core also holds our skin tissue biobank, which has been growing with the assistance of David Pease, our tissue acquisition specialist. Finally, we have a DNA/RNA Delivery Core, led by Dr. Irina Budunova and Dr. Alex Yemelyanov, and assisted by research associate Dr. Pankaj Bhalla; this core has generated lentiviruses for several dozens of faculty members, as well as for other cores, and now is specializing in using CRISPR/Cas technology for introducing genetic material into cells and tissues.
I also direct my own laboratory where a team is engaged in our in vitro and in vivo studies. I am fortunate to have a team of Dr. Xiaoqi Wang, research associate professor; four postdoctoral fellows (Drs. Dam, Bagnowski, Fogel and Liu); two technicians; and several students. Dr. Wang and two of the senior postdoctoral fellows help to supervise — each has his or her own projects, and everyone works as a team.
In the clinical research unit, we are fortunate to have faculty members who are experts in clinical trials administration: Dr. Dennis West, a dermatopharmacologist, and Dr. Stephanie Rangel. They work with me to oversee our pediatric dermatology research group of four MD fellows, a clinical coordinator, four gap-year students, and an administrative assistant, in addition to the infrastructure support of the entire department’s clinical research unit. Each fellow is the primary fellow for a few studies and supervises the students. We have so many clinical studies running that it really takes a team effort to make sure we have sufficient bandwidth for the detail-oriented work in taking care of the patients and all the documentation/regulatory tasks involved.