At the Garin-Shkolnik Lab, our research is dedicated to understanding the biological mechanisms underlying chronic inflammatory and rare skin diseases, with the ultimate goal of developing more effective, targeted, and long-lasting treatments.Led by Dr. Tali Garin-Shkolnik, MD, PhD, a dermatologist and physician-scientist at Rambam Health Care Campus, our research combines clinical insights with molecular biology, immunology, cellular metabolism, and translational medicine. Our work focuses on understanding why certain skin diseases develop, what sustains chronic inflammation, and why symptoms frequently return even after successful treatment.By investigating the complex interactions between immune cells, skin cells, and metabolic pathways, we aim to identify previously unexplored therapeutic targets and help translate scientific discoveries into future treatments.
The skin is much more than a protective barrier. It is a highly active biological organ, containing specialized immune cells, complex signaling networks, and metabolic systems that constantly interact to maintain tissue health.When these systems become dysregulated, they can contribute to persistent inflammation, abnormal cellular activity, and chronic skin disease.Despite remarkable advances in dermatological treatments, important questions remain unanswered. Why do some patients develop severe disease while others experience relatively mild symptoms? Why do certain treatments work exceptionally well for some individuals but not for others? And why can inflammation return to exactly the same location after the skin appears completely healed?Our research addresses these questions by studying the molecular and cellular processes that drive disease initiation, persistence, and recurrence.A central principle guiding our work is that understanding the mechanisms responsible for disease is essential for developing the next generation of therapies.Rather than focusing exclusively on suppressing visible inflammation, we seek to understand and eventually target the biological processes that allow disease to persist or return.
Psoriasis is one of the primary areas of our dermatological research.Affecting millions of people worldwide, psoriasis is a chronic, immune-mediated inflammatory disease characterized by red, thickened, and scaly skin lesions. Beyond its visible manifestations, psoriasis can significantly affect physical comfort, emotional well-being, and quality of life.Psoriasis is also associated with systemic inflammatory conditions, including psoriatic arthritis, obesity, metabolic syndrome, and increased cardiovascular risk.The disease develops through complex interactions between immune cells and keratinocytes, the predominant cells of the epidermis.A particularly important component is the IL-23/IL-17 inflammatory pathway, which contributes to immune activation, abnormal keratinocyte proliferation, and the development of characteristic psoriatic lesions.Modern biological therapies targeting these pathways have dramatically improved disease management. However, not all patients respond adequately, long-term treatment may be necessary, and disease frequently returns following treatment discontinuation.Our research therefore explores biological mechanisms beyond established inflammatory pathways, seeking to understand additional factors that contribute to disease severity, treatment response, and long-term persistence.We are particularly interested in identifying disease-associated molecular changes that may provide new opportunities for targeted therapeutic intervention.
One of the most intriguing characteristics of psoriasis is its tendency to recur in previously affected skin.Even after successful treatment restores an apparently normal appearance, the underlying tissue may retain biological changes associated with earlier inflammation.This phenomenon is often described as inflammatory memory or disease memory.Emerging scientific evidence suggests that certain immune cells, particularly tissue-resident memory T cells, can remain in the skin after visible lesions resolve. Other skin cells, including keratinocytes and stromal cells, may also preserve molecular changes associated with previous inflammatory activity.Together, these changes may create an environment that facilitates renewed inflammation when appropriate triggers are encountered.Our research investigates the cellular and molecular characteristics of skin that has undergone clinical remission, with particular attention to the relationship between immune memory, metabolic regulation, and inflammatory reactivation.Important research questions include:
● What distinguishes previously inflamed skin from skin that has never developed psoriasis?
● Which immune and metabolic pathways remain altered following successful treatment?
● Can persistent molecular changes help explain why psoriasis returns?Could targeting these processes reduce the likelihood or severity of future relapse?
Understanding inflammatory memory may help establish a foundation for therapies designed not only to control active disease but also to promote more durable remission.
T lymphocytes, commonly known as T cells, play a central role in protecting the body from infections and maintaining immune balance.Within the skin, specialized populations of T cells communicate with keratinocytes, other immune cells, and surrounding tissues through a sophisticated network of molecular signals.Under normal conditions, these interactions help preserve skin health. However, abnormal T-cell activation can contribute to chronic inflammatory disorders.Our research examines how T-cell behavior changes in diseased skin, how inflammatory signaling is maintained, and which cellular mechanisms may contribute to persistent immune activation.We are particularly interested in the communication between T cells and their surrounding microenvironment, including the influence of metabolic activity on immune-cell function.Investigating these relationships may reveal molecular pathways shared by different skin diseases and help identify therapeutic strategies capable of modulating disease-associated immune responses.This research also creates opportunities to explore connections between chronic inflammatory disorders and certain rare conditions involving abnormal T-cell populations.
Traditionally, inflammatory skin diseases have been studied primarily through the activity of immune cells and inflammatory signaling molecules.Increasingly, scientific research indicates that cellular metabolism is also an important regulator of inflammation.Cells require energy and molecular building blocks to grow, communicate, respond to environmental signals, and perform their specialized functions. These processes depend on tightly regulated metabolic pathways involving lipids, glucose, and other nutrients.Changes in cellular metabolism can influence immune-cell activation, inflammatory responses, and the behavior of skin cells.Our research investigates the relationship between lipid metabolism, metabolic regulatory pathways, and chronic skin inflammation.By examining how metabolic processes differ between healthy and diseased tissues, we seek to understand whether specific metabolic changes contribute to the maintenance of inflammatory activity.An important objective is to investigate how metabolic pathways interact with T-cell signaling and keratinocyte responses. This approach may uncover therapeutic opportunities that complement existing anti-inflammatory strategies by targeting disease-associated metabolic processes.
Alongside psoriasis, our research interests extend to rare and complex dermatological disorders for which effective treatment options may be limited.One important area is cutaneous T-cell lymphoma (CTCL), a heterogeneous group of cancers involving T lymphocytes that primarily affect the skin.Mycosis fungoides, the most common form of CTCL, may initially resemble chronic inflammatory skin conditions, making early diagnosis challenging in some patients.Although CTCL is fundamentally different from psoriasis, studying both conditions can provide valuable insights into T-cell biology, cellular signaling, and the skin microenvironment.Our research explores disease-associated molecular pathways and cellular characteristics that may distinguish malignant, inflammatory, and healthy skin tissues.We are also interested in rare inflammatory and keratinization disorders, including pityriasis rubra pilaris (PRP), where a better understanding of disease mechanisms could support the development of more targeted treatments.Comparative studies across different dermatological conditions may help identify both shared biological mechanisms and disease-specific therapeutic targets.Ultimately, understanding these similarities and differences could contribute to improved diagnosis, patient stratification, and future therapeutic development.
Our research integrates clinical observations with experimental studies designed to investigate disease at the cellular and molecular levels.Human skin tissue is particularly valuable because it enables the study of disease directly within its biological environment.Where appropriate and subject to ethical approval and informed consent, research using patient-derived skin samples can provide insights that cannot be fully reproduced in laboratory models alone.Our research approaches include several complementary areas.
Comparative examination of healthy, inflamed, and clinically resolved skin can help identify disease-associated molecular changes and reveal how different cell populations contribute to pathology.
Advanced tissue analysis techniques enable investigation of protein expression, cellular organization, and interactions between immune cells and surrounding skin structures.
Experimental cell models, including keratinocytes and immune cells, allow researchers to examine inflammatory responses, cellular signaling, and the potential roles of candidate molecular pathways.
Molecular profiling approaches can help identify changes in gene activity and metabolic regulation associated with disease development, persistence, and treatment response.
A defining feature of our work is its translational orientation.Translational medicine seeks to bridge the gap between laboratory discoveries and practical medical applications.For dermatology, this means connecting clinically observed problems with scientific investigations that may eventually lead to new diagnostic approaches, biomarkers, or therapies.Potential therapeutic strategies may include modulation of inflammatory pathways, regulation of disease-associated metabolic processes, and development of targeted treatments designed to act within affected skin.Locally delivered therapies are of particular interest because they may offer opportunities to concentrate treatment at affected sites while potentially limiting systemic exposure.However, identifying a promising molecular target is only the beginning of therapeutic development. Candidate approaches require extensive investigation to establish their biological effects, safety, formulation characteristics, and clinical effectiveness.Our long-term objective is to contribute to the scientific foundation required for developing therapies that address important unmet needs in dermatology.
Our research activities connect clinical dermatology with multidisciplinary scientific expertise.Dr. Garin-Shkolnik's combined background in medicine, molecular genetics, inflammatory biology, and translational research provides a foundation for approaching complex dermatological questions from complementary perspectives.Research activities are supported by collaborations and scientific interactions involving Rambam Health Care Campus and academic and research partners with expertise in immunology, molecular biology, advanced laboratory technologies, and therapeutic development.These connections help integrate clinical observations with experimental investigation and create opportunities for meaningful scientific collaboration.We believe that progress in dermatological research depends on combining different disciplines, technologies, and perspectives around shared scientific objectives.
Appropriate experimental models can support the investigation of disease mechanisms and the preliminary evaluation of therapeutic hypotheses before potential clinical development.By integrating multiple research methods, we aim to develop a more comprehensive understanding of disease biology and identify findings that warrant further validation.
The future of dermatology lies in a deeper understanding of the biological mechanisms that distinguish different diseases and individual patients.As molecular technologies continue to advance, researchers are increasingly able to investigate the complex relationships between immune activity, cellular metabolism, tissue organization, and chronic inflammation.Our vision is to contribute to this progress by identifying meaningful disease mechanisms and translating these insights into new therapeutic opportunities.We aspire to help advance a future in which treatments are not only effective at reducing visible symptoms but are also more precisely targeted, better tolerated, and capable of supporting sustained disease control.
From understanding the molecular origins of skin disease to exploring innovative therapeutic possibilities, our research is driven by a commitment to improving the future of dermatological care.
Our research programs are exploratory and translational in nature. Investigational therapeutic approaches discussed on this page are not necessarily available as approved clinical treatments.