AdvancesD I V I S I O N O F R H E U M A T O L O G Y SPRING 2015

Table of Contents

A Message from the Director .............................................................................................. 3

The Colton Center for Autoimmunity: Prospering Partnerships Between Medicine and Science ...........................................................................................................................4

The NYU Psoriatic Arthritis Center: A New Hub for Clinical and Scientific Progress .............7

Philanthropist Q & A with Jim Riley ..................................................................................... 9

Accelerating Medicines Partnership: How Knowledge of Abnormal Cellular Pathways Can Be Translated into New Therapies ...............................................................10

Working On A New Toolbox for Rheumatology ......................................................................13

Clinical Faculty Q & A with Brian Golden, MD .........................................................................15

Division & Faculty News .................................................................................................... 16

2015 Seminar in Advanced Rheumatology........................................................................ 18

List of Faculty ................................................................................................................... 19

Philanthropy ...................................................................................................................... 19

Research Cures Society Members .................................................................................... 19

Dear Colleagues and Friends,To flourish, an academic medical center must plant the seeds of success in fertile soil. Indeed, NYU Langone Medical Center’s Division of Rheumatology has an outstanding infrastructure of clinicians and scientists dedicated to the common goal of bringing discoveries to patients. At no greater time that now, has research been more productive and we are poised to harness this productivity for the many patients we serve. In addition to success with funding from both the NIH and advocacy groups, we are grateful to the philanthropy of our longtime donors who believe in our mission. And of course, the active participation of patients in partnership with our faculty has facilitated the approval of new treatments available to others across the nation and the world.

In this issue of Advances, we highlight some of the new initiatives and longstanding ties that continue to “seed” our success. With the generous backing of donors Judy and Stewart Colton, for example, we established the Colton Center for Autoimmunity in the summer of 2014. This comprehensive research program focuses on the link between the microbiome and autoimmune disease. This new direction provides a powerful platform upon which we can advance our goal of developing novel diagnostic, treatment and prevention options for patients.

With the generous support of The Riley Family Foundation and The Beatrice Snyder Foundation, we also launched our multidisciplinary Psoriatic Arthritis Center (PAC). The center, a bench-to-bedside integration of rheumatology and dermatology, will provide an unprecedented opportunity to understand how the disease progresses both biologically and clinically in patients with psoriasis.

In September 2014, the NIH selected the division to participate in another major new initiative called the Accelerating Medicines Partnership (AMP). This bold venture will help researchers uncover the cellular events that cause and perpetuate lupus nephritis and reveal the effects of race and ethnicity on disease mechanisms and drug targets.

All three efforts underscore the extraordinary partnerships we’ve formed and nurtured to advance our focus on fundamental research, state-of-the-art clinical care, and effective mentoring and education. These efforts comprise the very reasons why NYU Rheumatology is the perfect fit for researchers such as Johannes Nowatzky, MD, and clinicians such as Brian Golden, MD, both of whom are profiled in this issue.

We are honored that U.S. News & World Report recently ranked our Rheumatology program sixth in the nation, and that the division attracted more than $11 million in funding from private donations and $3.8 million in federal grants and contracts in 2014. These achievements have propelled visionaries such as the Colton, Riley, and Snyder families to partner with us in establishing an enduring series of exciting new programs that we project will yield dividends for years to come.

JILL P. BUYON, MD

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A Message from the Director

JILL P. BUYON, MD Director, Division of Rheumatology, Department of Medicine NYU Langone Medical Center

Front cover: An image of a human endothelial cell, part of studies by NYU Rheuma-tology team and the NYU Antiphospholipid Registry, showing that IgG antibodies from patients with the antiphospholipid syndrome stimulate the mammalian target of rapamycin complex (mTORC) an event that is associated with vascular injury.

(Specimen and Matched Phenotype Linked Evaluation), will help solidify the research infrastructure. To further clarify the events initiating autoimmu-nity, Dan Littman, MD, PhD, the Hel-en L. and Martin S. Kimmel Professor of Molecular Immunology, and Gregg Silverman, MD, professor of medicine and pathology, will lead molecular studies of the immune system’s T cells and B cells, respectively.

The center will primarily focus on specific immune responses to gastro-intestinal microbes. A link between chronic inflammation and commensal (“normal”) or pathogenic (disease-as-sociated) microbes has long been sus-pected, particularly in a variety of au-toimmune diseases. Although inflam-matory bowel diseases, such as Crohn’s disease and ulcerative colitis, are most clearly linked to the composition of the commensal intestinal microbiota, a potential connection to other autoim-mune diseases such RA, SLE, and APS has not been sufficiently studied. Such a link has been categorically demon-strated in mice, however, whether the intestinal microbiota composition influences the presence or absence of autoimmunity in multiple disease models is less well studied. In models of RA and multiple sclerosis (MS), for example, germ-free mice kept in cages devoid of any microorganisms are typically resistant to disease.

Dr. Littman’s lab identified the first commensal bacterium known to se-

lectively induce the differentiation of a specific subset of the immune system’s T cells (Cell, 2009). The microorgan-ism, segmented filamentous bacilli (SFB), sticks to the epithelial barrier lining the small intestine of mice and forms long segmented chains across the surface of the villi that project from the intestinal membrane. SFB colonization prompts naïve CD4+ T helper cells to differentiate into more

specialized cells that secrete cytokines. These cytokine molecules play impor-tant roles in protecting the intestinal epithelial layer from damage, but also can strongly promote inflammation. Because the cells produce a key cyto-kine called IL-17, this subset of T cells is known as Th17 cells.

Remarkably, the SFB-induced matu-ration of naïve T cells into Th17 cells makes certain mouse strains more susceptible to developing Th17-de-pendent arthritis or a form of mouse MS called experimental autoim-mune encephalomyelitis (Immunity, 2010). In mouse models, the onset of arthritis depends upon the produc-tion of self-reactive autoantibodies, and Th17 cells appear to facilitate the production of these antibodies. Th17 cells and autoantibodies are similarly thought to participate in the patho-genesis of human autoimmune dis-eases such as RA and SLE. A greater understanding of how the microbiota influence selection of the adaptive B and T cell immune repertoires may

prove crucial to revealing the first signs of autoimmunity.

In recently published studies, Dr. Lit-tman and colleagues characterized the antigenic specificities of Th17 cells present in the small intestine of mice colonized with SFB (Nature, 2014). Surprisingly, the majority of the Th17 cells reacted with proteins produced by SFB, while essentially no other T cells had such reactivity. This research raises several important questions: Why do SFB proteins induce only Th17 cells? Where does this process occur? And are SFB protein-specific Th17 cells the only mediators of autoimmune disease? In humans, researchers have reported the presence of bacteria bear-ing SFB-related sequences, but only in newborns; this finding will need to be confirmed through further char-acterization of the human microbiota with next-generation DNA sequencing technology. Despite some unanswered questions, the ongoing studies of how SFB interacts with the host’s adap-tive immune system are providing invaluable insights that will inform the Colton Center’s approach to studying human autoimmunity.

Although no one yet knows whether SFB possesses a similar ability to trigger autoimmunity in humans, Dr. Scher, Dr. Littman and Dr. Abramson found a striking association between newly diagnosed human RA and another intestinal commensal bacterium called Prevotella copri (eLife, 2013). Funded by a $4 million NIH grant, the NYU Langone collaborators used advanced technology not previously applied to autoimmune disease research: 16S and shotgun sequencing on stool samples from 114 rheumatoid arthritis patients and healthy controls. From the result-ing data, the study found that the pres-ence of Prevotella copri in fecal samples

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Launched in the summer of 2014, the Judy and Stewart Colton Center for Autoimmunity unites research, patient care, and education around the singu-lar goal of developing new approaches for diagnosing, treating and prevent-ing autoimmune diseases. At the heart of the center’s work is the growing realization that for many of these disorders, specific bacteria within the human microbiome may provide bio-markers of a pathogenic process that tips the scales toward overt disease in at-risk patients.

To tease apart the connections between our human microbiota and autoim-munity, the center’s two-phase plan is focusing initially on identifying the earliest events that lead to the develop-ment of several autoimmune diseases.

A better understanding of these mecha-nisms, in turn, can help researchers translate their lab-based findings into new diagnostic tools and therapeutics for the clinic. The plan will build upon recent discoveries by the NYU Langone team that have already linked certain microbes to new-onset rheumatoid ar-thritis (RA), and will capitalize on these observations to uncover potential mi-crobial triggers of systemic lupus ery-thematosus (SLE) and antiphospholipid syndrome (APS).

Steven Abramson, MD, the Frederick H. King Professor and chair of the Department of Medicine, will lead the center. Dr. Abramson has assembled a world-class team of physician sci-entists who will bring unparalleled interdisciplinary expertise to the

program. Jill Buyon, MD, the newly appointed director of the Division of Rheumatology and a world-renowned SLE researcher, and Jose U. Scher, MD, director of the NYU Langone Micro-biome Center for Rheumatology and Autoimmunity (MiCRA) and the lead author of recent studies linking the microbiome to RA, will collaborate in the investigations. As part of their sci-entific contributions, both researchers also will provide access to well-defined patient populations.

Michael Belmont, MD, associate direc-tor of clinical affairs for the Division of Rheumatology, will assist the center’s efforts by providing clinical expertise in APS. In addition, a critical division-wide pipeline of clinical data linked to biospecimens, known as SAMPLE

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The Colton Center for Autoimmunity: Prospering Partnerships Between Medicine and Science

“We now can study these autoimmune diseases simultaneously at the laboratory and clinical levels, and share our findings in a continual conversation. This is the kind of research that drives healthcare forward.”

—Steven B. Abramson, MD

strongly correlated with disease in new-onset untreated rheumatoid ar-thritis (NORA) patients upon their initial diagnosis. The researchers did not observe any similar association in healthy controls, in treated chronic RA patients, or in those with psoriatic ar-thritis. In the NORA patients, increases in Prevotella abundance correlated with a reduction in the abundance of Bacteroides bacteria and with a loss of reportedly beneficial microbes.

By integrating shotgun sequencing from the Human Microbiome Project with the NYU Langone cohort, the study found that the presence of Pre-votella genes correlated with disease—a discovery that may provide a useful diagnostic tool. Consistent with the early trends seen in humans so far, the researchers also found that Prevotella microbes able to colonize mice went on to dominate the intestinal microbi-ota and led to an increased sensitivity to chemical colitis, an animal model of inflammatory bowel disease.

The Colton Center will build upon such pioneering research with an ambitious two-phase strategy. In its first phase, the program will integrate novel fields of science and technology and expand collaborations between researchers and clinicians to enable transformative discoveries about the environmental triggers and seminal immunological events that character-ize the onset of autoimmune disease. By identifying the earliest events that drive autoimmunity, this research could lead to better strategies targeting both prevention and cure. This phase will include three overarching goals. First, the research is geared toward understanding and comparing the ear-liest immunological events that initiate the autoimmune responses in SLE, RA, and APS. Second, the project will

use advanced technology to identify microbial triggers of the immune sys-tem that initiate autoimmune disease in genetically susceptible individuals. And third, the collaborative effort aims to use these discoveries to devel-op novel strategies to treat and prevent autoimmune disease.

The subsequent research phase will be devoted to developing novel diag-nostics and therapeutics driven by the program’s basic science discoveries. This phase also includes three specific goals. First, the project will aid in the development of treatment strategies based upon the identification of dis-tinct molecular abnormalities of T cell and B cell activation that promote or perpetuate autoimmunity. Second, the program will study novel microbes and microbial proteins that could be potentially targeted for disease treat-ment and prevention. This arm of the collaborative effort will include strate-gies to prevent the interaction between microbial antigens and immune cells, as well as vaccine strategies to prevent colonization by microorganisms. Fi-nally, the Colton Center for Autoim-munity will identify and validate any serological or microbial events that precede disease. These telltale events can be exploited as prognostic or diagnostic biomarkers to determine who is at risk for autoimmune disease. Eventually, they also may lead to long awaited breakthroughs in early thera-peutic intervention.

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Up to 7.5 million Americans have psoriasis, according to the National Institutes of Health, making it the most prevalent autoimmune disease in the United States. Roughly 30 percent of those patients will develop psoriatic arthritis (PsA), leading to severe joint pain, stiffness and swelling. Although researchers have established a complex genetic basis for PsA, the susceptibility genes identified so far are neither nec-essary nor sufficient for disease onset, suggesting that environmental factors such as microbes may play a role.

NYU Langone Medical Center’s Pso-riatic Arthritis Center (PAC) was launched in 2014 to provide a better understanding of the biological and clinical course of disease. Led by the Division of Rheumatology in collabo-ration with the Ronald O. Perelman Department of Dermatology, the cen-ter’s integrated network of physicians and researchers also offers state-of-the-art care for PsA patients. “The best psoriatic arthritis care can be achieved only though an interdisciplinary and comprehensive approach to patients

with very specific needs,” says Jose U. Scher, MD, assistant professor of medi-cine and director of the PAC and the NYU Microbiome Center for Rheuma-tology and Autoimmunity (MiCRA).

PAC researchers are focusing on PsA’s initiating events in patients with pso-riasis. The resulting discoveries could form a strong translational base for developing new diagnostic, treat-ment and prevention tools. Dr. Scher, for example, is the lead author of re-cent studies linking the microbiome to new-onset rheumatoid arthritis (eLIFE, 2013) and to PsA (Arthritis & Rheumatology, 2015). In the latter study, he and colleagues found that PsA patients have less diverse com-mensal bacteria than either healthy volunteers or patients with psoriasis.

Soumya Reddy, MD, assistant profes-sor of medicine and dermatology and the PAC’s co-director, leads its database and clinical trial efforts. Dr. Reddy, a rheumatologist with extensive expertise in PsA clinical trials, is ex-amining the basis of gender differences in the disease. Female patients, she has found, have worse outcomes than male counterparts despite receiving the same medication (Arthritis & Rheuma-tology, 2014).

The PAC will also benefit from the PsA expertise of senior consultant Gary Solomon, MD, clinical associate professor of medicine. Annual pso-riasis and PsA meetings hosted by the center, including the NYU Langone PAC Seminar in Psoriasis and Psori-atic Arthritis, will give these experts and their international colleagues a platform to present cutting-edge ad-

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The NYU Psoriatic Arthritis Center: A New Hub for Clinical and Scientific Progress

Enhance

Clinical Cohorts &

Biorepositories

Identify Early & Preclinical

Disease

Determine Initiating Microbial

Triggers

Profile Earliest Autoimmune

Events (T/B Cell)

Select Targets for

Treatment

JUDITH AND STEWART COLTON CENTER FOR AUTOIMMUNITY

TRANSLATIONAL RESEARCH PIPELINE

New Pathways for Detection,

Treatment & Prevention of Autoimmune

Diseases

“If we are to truly achieve targeted, personalized medicine, we need to

partner the clinician with the basic scientist”. —Jill P. Buyon, MD

Jim Riley had a fast-paced career that he loved, until his painful psoriatic arthritis brought life to a near-stand-still. A patient of Dr. Steven Abramson since the mid-‘90s, Riley has benefited greatly from newer treatment options such as the blockbuster drug Remi-cade, initially developed at NYU Lan-gone. The grateful philanthropist talks about his longstanding relationship with the Division of Rheumatology and his decision to provide a leader-ship gift that helped launch the Psori-atic Arthritis Center (PAC).

What has motivated your long-term support of the Division of Rheumatology?

I’ve had psoriatic arthritis for over 25 years, and it got to the point where in the late ‘90s, it was hard to get up the subway steps. I spent my entire career at Goldman Sachs and I had to take a step back from work. I went on Remicade in 2002 and started to feel better, and then I went to Enbrel. Five years after I had retired, I was doing things that I never thought I’d be able to do again: I was swimming, I was cycling, and I set up a family office. I was also building a relationship with Dr. Abramson, who had spoken to me about some of the research. Our family

foundation is always looking for op-portunities that are leverage-able, and I think research is the most leverage-able way in the medical field to help as many people as possible. That’s how we got started.

Why is the Psoriatic Arthritis Center so important to you?

Psoriatic arthritis is a disease that takes a toll over time. So how do we get out in front of this? The stars are lining up for NYU to be the preeminent psori-atic arthritis center in the country, and I see how it can leverage the grants it’s already gotten. It’s not just about what we’re doing; I believe the opportunity is there for others to get in on the ground floor with us to propel the PAC to do exciting things.

What impact do you hope the center’s research will have for patients?

We’ve come so far but we have so much more to do, because it’s about quality of life. Are these diseases hereditary or not? These are the things we’re going to find out. My own family has had pso-riasis for many generations, and in one in three of us, it will turn into psoriatic arthritis. We just don’t know which ones, and doing the research ahead of

time to understand what triggers that can be huge. We’re investing in some-thing that is personal to our own fam-ily, and to many millions of others. At NYU, it feels like everyone’s going to be working together as a team, and we feel really good about the chances of posi-tive things happening.

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vances in both the clinical and basic science realms.

Under the guidance of Dr. Scher, Dr. Reddy and Dr. Solomon and with generous philanthropic support from The Riley Family Foundation, the PAC is focusing on five main clinical and research strategies:

First, the center will allow NYU Lan-gone’s PsA clinical program to expand its considerable reach and integrate expertise from rheumatology, derma-tology, radiology, orthopaedics and other specialties to diagnose and treat PsA patients. The PAC is part of the NYU Langone Center for Musculo-skeletal Care (CMC), the largest free-standing center of its kind in the U.S.

The PAC at CMC offers clinical man-agement and complex referrals for most new PsA patients and is a na-tional leader in clinical efficacy trials, longitudinal studies and mechanistic studies that relate PsA pathogenesis to therapeutic targets. Clinicians in the Division of Rheumatology already treat more than 900 patients every

year, including people from a wide range of ethnic and genetic back-grounds. The large and diverse patient pool provides a unique opportunity to better define new targets for personal-ized treatments.

Second, the center will investigate the natural history of psoriasis to under-stand the earliest events leading to PsA and other co-morbidities such as car-diovascular disease. These efforts will draw on the expertise of PAC faculty members such as Andrea Neimann, MD, assistant professor of dermatol-ogy, who studies the connections between psoriasis and cardiovascular disease and who co-directs NYU Lan-gone’s psoriasis clinical trials unit.

Third, the center will support an large roster of NIH-funded research efforts to identify more effective treatments and strategies to prevent and cure psoriasis and PsA. By examining the basic biology of joint and skin tissues and their dysregulation in PsA, for ex-ample, researchers may reveal the basic disease mechanisms that point toward novel therapeutics. Toward this end,

the PAC is collaborating with multiple immunologists at NYU Langone to investigate the molecular traits of auto-immunity-promoting T cells and how they contribute to the pathogenesis of both psoriasis and PsA.

Fourth, the PAC’s researchers are examining the role of the human microbiome in PsA development. As part of a $4 million NIH grant, NYU Langone launched MiCRA in 2009 to study the skin and gut microbiome in rheumatoid arthritis. In 2013, a sec-ond $547,000 NIH grant allowed the center to do the same for PsA. Ongo-ing efforts are studying the microbial residents of healthy volunteers and of patients impacted by rheumatic and autoimmune diseases. One potential outcome could be the development of new therapies such as prebiotics, probiotics, or other techniques to repopulate a patient’s intestinal tract with beneficial flora.

Finally, the PAC will enhance the op-portunities for academic-industry partnerships to help discover new PsA diagnostics, drug targets, and other

NYU Langone’s Center for Musculoskeletal Care

333 E 38th St, New York, NY 10016

Fourth floor lobby

The event will include a ribbon cutting ceremony, tours, and passed

hors d’oeuvres and cocktails

SAVE THE DATE

PSORIATIC ARTHRITIS CENTEROpening Reception

Thursday, June 4

6:30 to 8:00pm

therapeutic options. The center pro-vides a hub for NYU Langone’s Pso-riatic Arthritis Translational Registry and Biorepository, established in 2003 to store longitudinal clinical data and patient biospecimens. The bioreposi-tory already contains about 400 patient samples, making it one of the largest in the country and a key source of data for multi-center registries like the Pso-riatic Arthritis Research Consortium.

The PAC’s researchers are also col-laborating with multiple industry partners to identify biomarkers such as blood proteins, cells and molecules that may predict disease susceptibil-ity and determine whether or not patients respond to new therapies or experience drug toxicity. Simultane-ously, the PAC is teaming up with the Seligman Center for Advanced Therapeutics to help design, develop

and initiate multiple clinical trials investigating novel compounds and cutting-edge interventions.

Ultimately, the center’s complemen-tary efforts may clarify how PsA progresses in individual patients, how new therapeutics can be devel-oped and how those interventions can be personalized to maximize their potential benefit.

Profiles in Giving: Jim Riley

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Systemic lupus erythematosus, or SLE, is strongly associated with racial and ethnic disparities in disease severity and overall patient outcomes. In addi-tion, SLE is often accompanied by kid-ney inflammation; in extreme cases, lupus nephritis can lead to end-stage renal failure. In September 2014, the National Institutes of Health selected NYU School of Medicine to participate in a major new nationwide initiative that may help researchers uncover the cellular events that cause and perpetu-ate lupus nephritis and reveal the ef-fects of race and ethnicity on disease pathways and potential drug targets.

This initiative, the Accelerating Medi-cines Partnership (AMP), is a forward-thinking and bold venture involving the NIH, several major medical cen-ters, biopharmaceutical companies

and non-profit organizations. The goal is simple but lofty: to transform the current model of developing SLE diag-nostics and treatments by jointly iden-tifying and validating promising bio-logical targets of disease. The ultimate aim is to increase the number of new diagnostic and therapeutic options for patients and reduce the time and cost of developing them. The Division of Rheumatology is honored to have been selected as one of 11 centers to join this monumental effort. To maximize the impact of the clinical and tech-nological research, the Division has teamed up with colleagues from Albert Einstein College of Medicine and The Rockefeller University.

Jill Buyon, MD, will lead the NYU Lan-gone team, while Chaim Putterman, MD, and Thomas Tuschl, PhD, will

head up the Albert Einstein and The Rockefeller University teams, respec-tively. On the technological side, Dr. Tuschl brings extensive expertise and experience in coding and non-coding RNA sequencing analysis that can iden-tify unique patterns of RNA expression in tissues from lupus patients. This pat-tern identification, in turn, may lead to the development of RNA-based diag-nostics and therapeutics.

On the clinical side, Dr. Buyon and Dr. Putterman have long focused on SLE and currently treat more than 1,000 patients combined. For the partner-ship, they will assemble an ethnically and racially diverse group of SLE pa-tients who have nephritis as a major part of their disease. Under the broad-er umbrella of the AMP, the medical researchers will tap the wealth of clini-cal information contained within a patient cohort called the Multi-Ethnic Translational Research Optimization (METRO) Lupus Consortium. With this invaluable research tool, the team will develop, standardize and validate advanced technologies to identify criti-cal signaling pathways in patients’ re-nal and skin tissues, cells and urine.

The NYU Langone-led effort will call upon two additional clinicians with extensive expertise in the SLE field. H. Michael Belmont, MD, professor of medicine and Associate Director of Clinical Affairs in the Division of Rheumatology, directs the Bellevue Hospital Lupus Clinic, one of the old-est and largest clinics devoted solely

Accelerating Medicines Partnership: How Knowledge of Abnormal Cellular Pathways Can Be Translated into New Therapies

to the care of patients with SLE. Peter Izmirly, MD, assistant professor of medicine, directs a project sponsored by the federal Centers for Disease Control and Prevention, which aims to define the incidence and prevalence of SLE in Asians and Hispanics.

A third researcher, Robert Clancy, PhD, associate professor of medicine, will bolster the team’s scientific inves-tigations with his extensive experience in endothelial cell biology. Dr. Clancy, director of the biobank for SAMPLE (Specimen and Matched Phenotype Linked Evaluation, a new initiative to capture clinical and biologic informa-tion of patients with any rheumatic disease), will provide guidance in cell isolation techniques and work closely with The Rockefeller University.

With its seamless merging of clinical and technological expertise, the collab-oration is well positioned to conduct validation and longitudinal studies of new technologies and analytics, with an emphasis on development, re-sponse, flare and progression of lupus nephritis.

Because SLE is strongly associated with racial and ethnic disparities, the studies will address whether specific biological pathways and drug targets are dependent on race or ethnicity. Accordingly, METRO will include sub-stantial numbers of Black, Hispanic,

Asian, and White patients drawn from clinic populations at the NYU Hospital for Joint Diseases, Bellevue Hospital Center, NYU Langone Center for Musculoskeletal Care (CMC), and Gouverneur Hospital.

The “Multi-Ethnic” component of MET-RO also refers to the Division of Rheu-matology’s unique ability to care for patients of all ethnicities and races. “Our studies account for health disparities and facilitate discoveries that are applicable to people of varied backgrounds and socioeconomic status,” Dr. Buyon says. “Few places can match that.”

The AMP-METRO team’s focus on renal disease is driven by the major role of lupus nephritis in end-stage

renal failure. Underlying this effort is the premise that molecular analysis of gene expression and signaling in specific subsets of kidney cells may help predict the subsequent pathologic processes that lead to organ damage. Additionally, the research program may provide insights to deconstruct the complexity of SLE in general, and the histologic class of kidney disease in particular. Furthermore, any finding that a medically relevant pathway in renal tissue may be faithfully reflected in more readily accessible skin tissue, blood or urine could help link the disease phenotype to a “biotype” and pave the way to earlier identification and treatment options that are critical to renal survival.

The research initiative, in fact, could open up an entirely new realm of in-quiry that addresses the widespread vascular abnormalities that can de-velop in patients with SLE. Specifically, the team plans to evaluate whether dysfunctional activation of cells lining the blood vessels in the tubules and interstitial tissue of the kidney in lupus nephritis is accompanied by a similar activation in other vascular locations

“We will be using patient samples such as kidney and skin biopsies to look for targets and pathways that would

be coverable by new biologics; as with the Colton Center, it’s ultimately about better therapeutics for

patients living with these diseases.” —Jill P. Buyon, MD

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such as those in a patient’s unaffected skin. By also analyzing specific types of circulating blood cells, the research should help clinicians determine how to apply existing and future therapies to predefined patient populations.

The field needs such clinically relevant information. Treatment of kidney nephritis is traditionally considered a two-phase process: induction and maintenance. Induction uses high doses of immunosuppressive or cytotoxic agents in conjunction with high-dose glucocorticoids to reverse the immune-mediated inflammatory processes. Maintenance therapy consists of lower and presumably safer levels of immuno-suppressive medications to assure a last-ing response and prevent recurrences. Despite aggressive induction therapy, however, nearly half of all patients do not achieve either partial or complete remission within 6 months. Even if treatment is continued for 12 months, the overall response rates are similar.

Although the U.S. Food and Drug Administration recently approved the monoclonal antibody belimumab to treat extrarenal SLE, no new therapies have been approved for lupus-associated kidney inflammation in over fifty years. Approved drugs for SLE – including aspirin, hydroxychloroquine, and corti-costeroids – have fallen short of expecta-tions for the kidney due to their lack of efficacy or unacceptable side effects.

Researchers have offered several expla-nations for why the field hasn’t made more progress in treating nephritis. First, current drugs are not logically aligned with the pathogenic stage of disease. For example eliminating auto-reactive B cells might have little impact if the strategy is used during a comple-ment-mediated acute flare, although this approach may prevent future flares. The NYU Langone effort will address disease stages in the METRO cohort by conducting comprehensive clinical and laboratory evaluations ev-ery 2 months to monitor disease activ-ity and treatment responses.

Second, the slow progress in drug development may be due in part to the absence of a standard definition of complete response, which can con-found interpretations of efficacy. The METRO cohort-based analysis will ac-count for this wrinkle by recording all clinical variables and comparing cur-rent definitions of complete response to assess how they correlate with iden-tified biological pathways.

Third, treatment response may be highly influenced by ethnic and ra-cial differences. For patients with proliferative forms of lupus nephritis, renal survival is worse in Black and Hispanic patients despite aggressive treatment with intravenous cyclo-phosphamide – even after control-

ling for hypertension, initial renal impairment, and corticosteroid dose. Socioeconomic features such as in-come, educational level and access to health care may contribute to the poorer prognosis in some of these populations. In one study, however, the relative risk of progression to end-stage renal disease remained high in Hispanics even after adjusting for these risk factors. METRO will enroll ethnically and racially diverse patients to address possible pathophysiologic changes that increase the risk of pro-gression to end-stage renal disease in minority populations with nephritis.

Finally, a significant limitation of cur-rent strategies relates to the mantra, “Time is kidney.” Several studies have demonstrated that delays in obtaining a renal biopsy or in initiating treat-ment can negatively impact patient outcomes. As part of the new effort, a longitudinal METRO cohort will provide a unique opportunity to ad-dress whether specific gene expression or signaling pathways in unaffected skin, circulating blood cells, or cells shed through urine parallel or even precede the molecular warning signs in the kidney. If so, these less invasive biomarkers may trigger an earlier renal biopsy and lead to more specific and potentially lifesaving treatment.

When Johannes Nowatzky came to NYU, he brought with him an interest in an unusual disease — Be-hcet’s. “It’s an inflammatory disease,” Nowatzky says, that’s rare in the US, but common to many Middle East-ern and Asian countries.

Nowatzky, a German native, did his residency in Israel, where he saw patients with Behcet’s disease at a na-tional referral center on a daily basis. He came to NYU for a Rheumatology fellowship in 2009 and he has found New York City has more than its fair share of Behcet’s, thanks to its diver-sity of ethnic patient groups.

Now he has a thriving research pro-gram that seeks to develop a cell-based immunotherapy for Behcet’s and other autoimmune diseases. “It’s meant to alter the immune system in a way that cures disease — or at least alleviates disease,” Nowatzky says. He hopes his work prompts other clinical research-

ers to consider cell-based treatments for other rheumatological diseases.

“Every cancer specialist knows what cell-based immunotherapy is and many people in infectious disease do as well,” he says. “I want to introduce the notion of this form of treatment into our field. That’s the number one goal of my research.”

Behcet’s disease is an autoimmune disorder that causes inflammation and damage to blood vessels in the body. It is commonly seen in the interior lining of the eye — the uvea —which includes structures such as the colored iris in the front and the layer immediately beneath the retina in the back of the eye. Behcet’s almost always causes mouth ulcers and often skin rashes. Some patients have life-threatening disease of large blood ves-sels, the brain or other organs.

Nowatzky’s research focus is on those components of the immune system that have suppressive effects. “With infection” — the classic immune response scenario — “the immune system provides the means to fight,” he says. “But you also get collateral damage or have the system shoot into the wrong direction.” The suppressive

elements of the immune system are there to curb overly strong, prolonged or misdirected immune responses and to bring the fight to cessation.

By manipulating the suppressive side of the immune system, Nowatzky thinks he can dampen the autoim-mune reaction in diseases like Behcet’s. He says there’s potential for the strat-egy to be used in other, more common autoimmune diseases, such as mul-tiples sclerosis and type-I-diabetes.

Specifically, Nowatzky studies immu-nosuppressive players known as regu-latory T cells. “We know these T cells control the immune system and can regulate potentially harmful immune responses,” he says. And this knowl-edge leads to a number of research questions. “Are these cells different in people with autoimmune disease?

Working On A New Toolbox for Rheumatology

“It’s meant to alter the immune system in a way that

cures disease — or at least alleviates disease”.

“The “multi-ethnic” component of the name also reflects the unique ability of the division to care for

patients of all ethnicities and races. Our studies account for health disparities and facilitate discoveries

that are applicable to people of varied backgrounds and socioeconomic status.”

A leader in quality care,

NYU Langone was

ranked number one in

2013 & 2014 for overall

patient safety and

quality among leading

academic medical

centers across the nation

that participated in the

University HealthSystem

Consortium HC) Quality

and Accountability Study

Dr. Brian D. Golden, Clinical Associ-ate Professor in the Department of Medicine, came to NYU 20 years ago to do a fellowship at the Hospital for Joint Disease, and he has stayed ever since. He says that rheumatologists are a bit like super internist, because they tackle a large number of differ-ent conditions and face patients with a mix of medical issues, including chronic and complex conditions. He doesn’t see many run-of-the-mill textbook-cases, in other words. For Golden, this reality is a challenge that keeps his rheumatology practice both interesting and rewarding.

Here Golden talks about why NYU Rheumatology is the perfect fit for him.

Why did you choose Rheumatology?

I was influenced by a mentor I had when I was a medical student at Mt. Sinai School of Medicine. One of my attending physicians on the wards was a well-known rheumatologist named Harry Spiera. I was very im-pressed both by him and some of the cases we saw.

The interesting thing about rheuma-tology is that you see complex diseas-es and diagnostic puzzles. You don’t get much hard data, as from a simple diagnostic test. Rather you have to put it all together from the clinical presen-tation and the patient’s history.

Are those things that drew you to Rheumatology as a medical stu-dent still present in your daily practice?

Yes, absolutely. It’s still why I find it interesting. It’s a clinically based field, and also it’s so broadly based that it overlaps with many other specialties. We truly have to be the best internists and understand all the organ systems well. There are so many different kinds of clinical presentations, that you have to be good at thinking through all the possible diagnoses.

What has changed in the field of Rheumatology over your career?

There are two things, two realms that really that didn’t exist back when I was a medical student. One is care in osteoporosis. For many years, this was not on the rheu-matology radar screen — it usually was an endocrinologist’s case or a gynecologist’s case. Each specialty looks at it from a different perspec-tive: rheumatologists see it as a skel-etal disease, a disorder of bone and skeletal function; endocrinologists see it as a calcium metabolism prob-lem, encompassing nutrition and parathyroid involvement; and gyne-cologists see it as a common problem in postmenopausal women.

The fact is that bone is a dynamic tis-sue. We rheumatologists see the pa-tient as a whole. We pay attention to the joints and cartilage and to events that are upstream from bone turnover and metabolism.

The second area is muscular skeletal ultrasound. It’s the same ultrasound technology that radiologists and gy-necologists use, but we use it to look at joints and ligaments and tendons — those structures inside the body that we can’t see otherwise. This means

Page 15nyulangone.orgPage 14 ADVANCES / SPRING 2015

Clinical Faculty Q&A with Brian Golden, MDWhat controls the balance between regulatory and effector T cells? What are self- and other antigens that these cells recognize?”

At the end of the list is the big goal: Can the answers to any of these ques-tions be translated into a treatment for patients?

Cell-based therapies typically involve taking the patients’ own cells and ma-nipulating them in some way – often outside of the patient’s body. Then the cells are injected back into the patient where they are expected to exert their new and improved functionality.

Nowatzky is at the beginning stages of developing his regulatory T cell therapy. “These cells are relatively few in the body,” he says. So far his work has been to develop methods to grow large numbers of ultra-pure human regulatory T cells in vitro while main-taining their functionality. “We exam-ine their stability, their effectiveness, and how they function.”

Recently, he has started to test patient-derived cells in a “humanized” animal

model, to show their safety and effec-tiveness in a living organism. Nowatz-ky is using a new model of graft-vs-host disease in severely immunosup-pressed mice that can tolerate and engraft human cells as an in vivo proof of principle step. Only then can he take the next step and get approval to test his cell-based therapy in humans.

Nowatzky finds NYU to be a particu-larly rich environment for his ambi-tious and open-ended research pro-gram, and not only because it’s in one of the most ethnically diverse cities in

the world. He makes sure to keep up his clinical practice, serving one full clinic day each week.

“As a clinical researcher, I find my work very fulfilling and rich,” he says.

He values the good access to a broad array of excellent investigators in the Division of Rheumatology and beyond, namely the immunologists working at the Skirball Institute of Biomolecular Medicine and other researchers in the Department of Medicine. He appreciates the admin-istrative support and the availability of internal funds to keep his research program going in between grants.

“The problem with NYU is that it’s big. The advantage of NYU is that it’s big.” Nowatzky cites his 20-min walk from his office to his lab, as a tiny downside compared to the huge potential of a place of this size. And he’s not found any barriers to cross-ing divisional or departmental lines. “There are endless opportunities here, if you’re willing to look for them,” he says. “And I definitely have the free-dom to do that.”

“The fact is that bone is a dynamic tissue. We rheumatologists see the patient as a whole.

We pay attention to the joints and cartilage and to events that are upstream from

bone turnover and metabolism.”NYU Langone has

390 physicians named

on Castle Connolly’s

“America’s Top

Doctors” and

New York magazine’s

“Best Doctors”

annual listings

Page 17nyulangone.orgPage 16 ADVANCES / SPRING 2015

we can ask more detailed questions. What’s going on in bursitis? What activity can we see in inflammatory rheumatoid arthritis? Is there evi-dence of early bone erosion? Ultra-sound also helps with guiding doctors through procedures, allowing us di-rect visualization as we place a needle into a joint, for instance.

Ultrasound methods are increas-ingly becoming part of the teaching program here at NYU. Dr. Jonathan Samuels is leading that effort and I’m part of the core team who has experience with the technology and

is currently teaching it as part of the academic mission of NYU to train students, interns and fellows in the latest methods.

What are the strengths of Rheumatology at NYU?

When I was at Mount Sinai as a medi-cal student and a resident, I worked with Dr. Spiera and learned so, so much. But I wanted to go someplace else for my fellowship, partly for the very practical reason of having change of scene. One big attraction of NYU was that its program in rheumatology

was much bigger and much broader. And I have stayed here because the atmosphere is great — the research side and the clinical side of rheuma-tology are well-balanced and there’s really smart people on both sides of the equation.

What sort of patients do you see in your practice?

I’m a general rheumatologist, so I see it all. I think I’m a good clinician and diagnostician. I see patients with osteoarthritis, rheumatoid arthritis, psoriatic arthritis, lupus, fibromyalgia, vasculitis, inflammatory muscle dis-ease, osteoporosis, and gout.

I feel comfortable taking care of every one of these patients. Also, in the Divi-sion of Rheumatology at NYU, there is always a colleague across the hall to consult with on complex cases. We all do this all the time. We put our heads together and find the best solutions for our patients.

We are proud to report that the 2014-2015 U.S. News & World Report ranked our Rheumatology program as #6 nationally, up from #7 in 2013.

Dr. Ashira Blazer, a Second Year Fellow, was awarded the Rheumatol-ogy Research Foundation’s Scientist Development Award for her project entitled “Arterial dysFunction Re-lated to INF in Carriers of APOL1” (AFRICA). With this grant, Dr. Blazer will study mutations in the Apolipoprotein L1 (APOL1) gene

which associate with non-diabetic renal disease—including lupus ne-phritis, and cardiovascular disease in homozygous carriers of African ancestry. This study will leverage two Systemic Lupus Erythematosus (SLE) cohorts: one African Ameri-can and one Ghanaian to address this inquiry through the develop-ment of parallel biorepositories. NYU will consequently cultivate the first African SLE biorepository, which will be instrumental in iden-tifying ethnically determined prog-nostic factors in lupus.

Dr. Svetlana Krasnokutsky-Sam-uels was awarded a prestigious, three-year American College of Rheumatology/Rheumatology Research Foundation Investigator Award. This award will support her studies on the use of colchicine for the treatment of osteoarthritis.

Dr. Johannes Nowatzky received a five-year K08 award from the NIH/National Eye Institute. This award is intended to provide an opportu-nity to promising medical scientists with demonstrated aptitude to

Division & Faculty News

develop into independent investi-gators. This funding will support Dr. Nowatzky’s work on harnessing monoclonal Treg for the treatment of autoimmune uveitis.

On Thursday, April 23rd NYU hosted the Arthritis Foundation Research Forum. The forum, with an introduction by Rheumatology Division Director Dr. Jill Buyon, featured Arthritis Foundation (AF) funded “Young Investigators” from several institutions throughout the region, presenting their findings in an effort to facilitate breakthroughs in arthritis research. NIAMS Direc-tor Stephen I. Katz gave a special introduction, and our own Dr. Jose Scher served as the Keynote Speaker.

Dr. Jill Buyon received a 5 year R01 grant for her ongoing clinical trial entitled “Preventive Approach to Congenital Heart Block with Hy-droxychloroquine” (PATCH). This study, which was previously funded by a Lupus Foundation of Min-nesota research grant, an NIH R03, and a Lupus Foundation of America LIFELINE Award, is a first-ever evaluation of whether hydroxychlo-roquine, a drug widely used for SLE, prevents recurrent congenital heart block. The R01 will fund the second stage of study enrollment as well as a second aim that addresses the oph-thalmologic safety of hydroxychloro-quine exposure during pregnancy.

Dr. Peter Izmirly was an invited contributor to the National Public Health Agenda for Lupus confer-ence in Washington D.C., spon-sored by the Lupus Foundation of

America and the National Associa-tion of Chronic Disease Directors and funded through a grant from the Centers for Disease Control and Prevention (CDC). This was the first time lupus and public health experts came together to talk about the urgent needs of people with lupus and their families. During the conference, Agenda contributors formulated 20 recommendations and corresponding strategic actions. The Agenda is currently being drafted and circulated for comment, and it is anticipated that it will serve as a blueprint for action after final approval by the CDC.

Dr. Jonathan Samuels has been se-lected as physician chair of the 2015 Arthritis Foundation’s Walk to Cure Arthritis in NYC. This signature event of the Foundation unites com-munities across the country to help put an end to arthritis. Donations are used to help patients gain access to the critical medications necessary to live full, healthy lives and to fund research that provides better treat-ments today and promises a cure for tomorrow. This year’s walk will be across the Brooklyn Bridge and take place on Saturday, May 16th.

Fellowship News After the fall fellow-ship interview season, the Division was pleased to have a very successful match and looks forward to welcom-ing our new rheumatology fellows this summer. In addition, thanks in part to a supplemental grant from the Ameri-can College of Rheumatology (ACR), we are increasing the program to 4 fellows per year.

Dr. Michael Pillinger, our Rheuma-tology Fellowship Program Director, received the ACR Distinguished Program Directors Award at the 2014 Annual Meeting in Boston. Dr. Pillinger is also a member of the ACR Board of Directors, Chair of the ACR Curriculum Task Force, and Chair of the ACR Basic and Clinical Science Training Curricu-lum Committee.

Two of our faculty members ob-tained full professorship. Dr. Michael Belmont, Professor of Medicine (Clinical) and Dr. Michael Pillinger, Professor of Medicine (Clinical) were honored at the 1st Annual Recogni-tion Reception for Department of Medicine Appointments and Promo-tions, held at the Water Club.

Dr. Adam Mor was awarded an In-novative Research Grant from the ACR Rheumatology Research Foun-dation (RRF). Dr. Mor will be study-ing the role of PD-1 (Programmed Death-1) signaling in T cells in Rheu-matoid Arthritis, using both human cells and murine models. These stud-ies may ultimately lead to new immu-nomodulatory targets, and will shed light on the current processes leading to immune activation in RA. He will be joined in his efforts by Drs. Bruce Cronstein and Gregg Silverman who will serve as collaborators. This grant builds upon a related study currently funded by the RRF.

Division & Faculty NewsNYU Langone is the only hosptal in New York to receive

top 10 rankings all three musculoskeletal specialty

areas of orthopaedics, rheumatology, and rehabilitation in

U.S. News & World Report’s Best Hospitals ranking.

Shahla Abdollahi-Roodsaz, PhDSteven Abramson, MDMukundun Attur, PhDNatalie Azar, MDBertha Bauer, MDH. Michael Belmont, MDStephen Bernstein, MDNina Bhambhani, MDLenore Brancato, MDJill Buyon, MDFranco Celada, MD, PhDEfstathia Chiopelas, MDRobert Clancy, PhDMichael Colin, MDBruce Cronstein, MDMark Eberle, MDSari Edelman, MD

Page 19nyulangone.orgPage 18 ADVANCES / SPRING 2015

Philanthropy2015 Seminar in Advanced Rheumatology

Become a member of the Research Cures society and help NYU Langone’s Division of Rheumatology maintain excellence in patient care, research and education.

The Division of Rheumatology is filled with talented and devoted faculty mem-bers who provide exceptional patient care, produce groundbreaking research, and educate future generations of medical professionals. The partnership and support of our donors and friends are essential ingredients in assuring our standard of excellence as we serve the health care and wellness needs of the thousands of lives we touch each day.

If you would like to make a gift to the Division of Rheumatology, please call Me-lissa Y. Sosa, Director of Development, and join us as we raise the bar in health care here and beyond our campus.

To reach Melissa Y. Sosa, call 212-404-3510 or email melissa.sosa@gmail.com.

Avram Goldberg, MDBrian Golden, MDStephen Honig, MDPeter Izmirly, MDPhilip Kahn, MDSara Kramer, MDSvetlana Krasnokutsky-Samuels, MDSicy Lee, MDEuna Lee, MDKristen Lee, MDPaula Marchetta, MDKavini Mehta, MDHal Mitnick, MDAdam Mor, MDJohannes Nowatzky, MDMark Philips, MD

Michael Pillinger, MDAndrew Porges, MDPaula Rackoff, MDSoumya Reddy, MDPamela Rosenthal, MDJonathan Samuels, MDJose Scher, MDHarry Shen, MDGregg Silverman , MDStephen Smiles, MDBruce Solitar, MDGary Solomon, MDChung-E Tseng, MDStelios Viennas, MDGerald Weissmann, MDYusuf Yazici, MDGary Zagon, MD

RESEARCH CURES SOCIETY MEMBERS

LIST TO COME?

Division of Rheumatology Faculty, NYU School of Medicine

BOARD MEMBERS

The annual NYU Seminar in Advanced Rheumatology took place in March 2015 and attracted rheumatologists, orthopedists, trainees in the rheumatic diseases and internists with a special interest in rheumatology.

Division of Rheumatology 301 East 17th Street, Suite 1410 New York, N.Y. 10003

nyulangone.org 212-598-6110