Our team conducts a wide variety of research focused on psoriasis and psoriatic arthritis (PsA), the microbiome’s role in autoimmunity, and the mechanisms underpinning other immune-mediated inflammatory diseases.

Psoriatic Arthritis Research

Our research, which is performed as part of the Psoriatic Arthritis Center (PAC), seeks to discover novel psoriasis and psoriatic arthritis (PsA) targets, improve prevention options in at-risk populations, test combination therapies, and address pain and other quality of life issues. In many cases, changes in the microbiome can provide meaningful biomarkers or other information about whether and how interventions affect the underlying dysbiosis.

Our PsA research has focused in large part on our PROGRESS (Psoriatic Response and Onset: Genes Radiology Environment Skin and Synovium) Cohort. In particular, we are working to improve our understanding of the natural history of psoriatic disease and to characterize the immune, environmental, and molecular events that precede PsA onset. With this knowledge, we can seek out new preclinical interventions that delay, attenuate, or even prevent PsA development in at-risk patients with psoriasis, such as with the ongoing PAMPA multicenter study, which is being led by Rebecca Haberman, MD, MSCI. The first trial of its kind, it is an investigation into whether a biologic disease-modifying antirheumatic drug (DMARD) in high-risk psoriasis patients can prevent progression of psoriasis to PsA when compared to placebo and to other standard of care treatment.

With the invaluable help of our collaborators, we are also exploring a wide range of other strategies to improve psoriatic disease outcomes beyond the limits of current therapies. These are among our many translational goals :

• discover novel inflammatory pathways and cell subsets that may provide new therapeutic targets and biomarkers of disease progression (in collaboration with the lab of Shruti Naik, PhD)
• apply stratification biomarkers to individualize therapy (in collaboration with the lab of Ashleigh Theberge, PhD, at the University of Washington)
• test combination therapies to determine if we can improve PsA responsiveness as part of the AFFINITY study
• address comorbidities, chronic pain, and fatigue in PsA patients, including visualizations of residual pain and depression via fMRI and an investigation of synovial pathotypes (led by Dr. Haberman)
• assess lifestyle modifications as a complementary approach to improving patient outcomes.

To further our research, we’ve made extensive use of the Psoriatic Arthritis Translational Registry and Biorepository (PROGRESS), which we established in 2003, as well as emerging technology. In close collaboration with the Naik Lab, for example, we’ve used spatial transcriptomics, a new technology that can determine gene expression by its cell type and histological location, to distinguish between mild and severe forms of psoriasis through the activity of certain immune and inflammation-regulating cells and key signaling pathways.

We saw a different pattern of fibroblast and macrophage cells in the upper layers of affected skin in more- severe cases of psoriasis than in milder cases or in the healthy skin of unaffected counterparts. We also documented significant increases in gene activity within more than three dozen molecular pathways linked to metabolism and control over lipid levels.

Dr. Haberman is leading multiple projects in this research arm of the lab. Read more about her projects.

Microbiome Research

Our lab’s microbiome research explores the potential pathways by which microbes may trigger psoriasis, PsA, and other autoimmune and immune- mediated diseases (AIMDs). In addition, we are studying how the microbiome’s stew of drug-metabolizing enzymes might alter a patient’s response to traditional therapies, such as methotrexate, or predict whether a certain regimen will be effective. To identify potential therapeutic strategies, we’re assessing the effects of commensal bacteria or their metabolites on lab models of PsA.

This line of research has been greatly aided by the NIH-funded NYU Microbiome Center for Rheumatology and Autoimmunity (MiCRA). Since its inception in 2009, MiCRA has enrolled hundreds of healthy participants and volunteers with rheumatoid arthritis (RA) and PsA and collected thousands of blood, fecal, oral, and skin samples.

Dr. Blank is leading multiple projects in this research arm of the lab. Read more about her projects.

Immune-Mediated Inflammatory Disease Research

Within our lab’s research portfolio, we’re also exploring whether the gut microbiome can be altered to accelerate an effective initiation of methotrexate therapy in RA patients. Similarly, we’re investigating the potential effects of bacterial short-chain fatty acids on gut microbes and the regulatory immune response in RA patients. Our research has benefited enormously from the largest and most comprehensively phenotyped rheumatoid arthritis (RA) cohort in the United States. In addition, our new-onset rheumatoid arthritis (NORA) cohort has provided further insights about microbiome changes in this population of those with RA.

Some of our basic and translational research in this area is conducted under the auspices of NYU Langone’s Judith and Stewart Colton Center for Autoimmunity, which seeks to better understand the immunological basis of autoimmune disorders. In collaboration with Bettina Nadorp, PhD, for example, we are building a predictive tool of treatment response to TNFa inhibitors (TNF-i) based on disease-agnostic molecular biomarkers derived from single-cell profiling of peripheral blood mononuclear cells in patients with inflammatory bowel disease, PsA, and RA.

Our other areas of focus in immune-mediated inflammatory disease (IMID) research include multiple studies on the effects of COVID-19, including a web-based assessment of autoimmune, immune-mediated, and rheumatic patients during the pandemic and an analysis of the incidence of COVID-19 in IMID patients. We have also investigated the effects of immunomodulatory therapy on COVID-19 susceptibility and clinical outcomes.

Research Led by Rebecca Haberman, MD, MSCI

Psoriatic Arthritis–Related Pain and Depression

Up to 50 percent of patients with seemingly well- controlled PsA continue to have joint pain, but the etiology of this persistent pain is not well understood and is likely not solely driven by inflammation. Dr. Haberman’s research aims to define the prevalence, phenotype, and clinical drivers of persistent pain, including contributing factors such as depression, anxiety, sleep disturbances, and coping mechanisms. Depression is of particular interest, as it is seen in up to one-quarter of patients with psoriatic arthritis at NYU Langone and is associated with decreased likelihood of achieving disease remission.

In collaboration with neuroradiology colleagues, Dr. Haberman is also using brain fMRIs to try to visualize and quantify noninflammatory pain and its drivers, in part by characterizing neuroconnectivity differences between patients in full remission and those with persistent joint pain.

The ultimate goal of this research is to develop personalized nonpharmacologic interventions to the identified targets as adjuvants to immunomodulatory therapy to improve patient outcomes. In addition to her work at NYU Langone, Dr. Haberman is part of a national consortium examining pain mechanisms in PsA and other immune-mediated inflammatory diseases.

Prevention and Early Treatment of Psoriatic Arthritis

Dr. Haberman is the lead investigator of the Preventing Psoriatic Arthritis Cohort, which follows patients with psoriasis to better explore the factors that play a role in progression from psoriasis to PsA, and of PAMPA, which is the first clinical trial to look at the use of biologics in patients with psoriasis to prevent progression.

Other Psoriatic Arthritis–Related Projects

Dr. Haberman’s other research interests include the use of digital health applications and wearables to monitor PsA symptoms and early response to drug therapy. She is also working to understand differences in disease presentation and phenotype in racially and ethnically diverse patients. In addition, she is seeking to identify the impact of COVID-19 infection and vaccination on patients with immune-mediated inflammatory disease, understand the transition from psoriasis to psoriatic arthritis, and better characterize the psychosocial impact of psoriatic disease.

Research Led by Rebecca B. Blank, MD, PhD

Microbiome and Inflammatory Arthritis

Dr. Blank’s research focuses on the role of the gut microbiome in the pathogenesis and amelioration of inflammatory arthritis, particularly rheumatoid arthritis (RA). Two ongoing studies are attempting to elucidate the role of the gut microbiome and its metabolic products, such as short chain fatty acids (SCFA), in inducing a regulatory immune response in patients with RA.

One study is a proof-of-concept trial of the potentially beneficial role of SCFA supplementation in patients with new onset RA. The other focuses on patients with RA who have an inadequate response to methotrexate therapy. Participants will take an oral SCFA supplement for up to four months in order to assess changes in their gut microbiota, blood and stool metabolites and inflammatory immune cell types before and after treatment.

Other Projects

Dr. Blank is also a co-investigator in the NIH-funded Accelerated Medicine Partnership (AMP)Microbiome Technology and Analytic Center Hub (Micro-TeACH) and is collaborating on projeect with multiple principal investigators to determine predictive biomarkers of TNF alpha responsiveness in patients with RA or psoriatic arthritis.

Research Led by Catherine R. Howe, MD

Preventing Arthritis in a Multi-Center Psoriasis At-Risk Cohort (Multi-Center PAMPA Study)

Dr. Howe is the NYU site lead for the PAMPA study, which is the first clinical trial to evaluate the efficacy of biologics in preventing the progression from psoriasis to psoriatic arthritis. Specifically, it is a multicenter, randomized, placebo-controlled trial of guselkumab (Tremfya) compared to non-biologic standard of care in high-risk psoriasis patients.

NYU Psoriasis and Psoriatic Arthritis Twins Study (PATS)

Dr. Howe is a co-investigator for the PATS study, which is a longitudinal study of monozygotic twins discordant (and concordant) for psoriatic disease. Study participants are seen every 1-2 years at the NYU Psoriatic Arthritis Center to assess for disease activity/progression and to collect biosamples (blood, urine, stool, skin samples). Clinical and biologic data will be used to investigate potential epigenetic, microbiomic, metabolomic, and transcriptomic differences between affected and unaffected twins, in order to better understand disease pathogenesis.