Division of Rheumatology

New Directions in Lupus Research

BRONX, NY - February 16, 2015 - Dr. Chaim Putterman, Professor of Medicine and of Microbiology & Immunology and Chief of the Division of Rheumatology, is currently studying whether a molecule known as TWEAK (TNF-related weak inducer of apoptosis) or other potential mediators of inflammation can act on brain cells to promote some of the neurologic signs and symptoms that lupus patients suffer from, and whether in experimental systems they can be treated or prevented. These particular studies, for which Dr. Putterman was recently awarded a large grant by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, draw from his extensive history of research into lupus-related abnormalities of the immune system and how they present in tissues and organs throughout the body.  

This article is the first in a series exploring Dr. Putterman’s research to bring about significant advancements in diagnosing and treating lupus, and improve the quality of life and short- and long-term prognosis of patients affected by this disease. 

Part I: Chance Favors the Prepared Mind

In many of his research studies, Dr. Chaim Putterman has used one or more different strains of mice, each of which is known to spontaneously develop a pervasive autoimmune disease that imitates many aspects of human lupus. Along the way, minor laboratory “accidents” involving these mice have informed and shaped the direction of Dr. Putterman’s work.

Earlier in his career at Einstein, while working to identify why certain patients with lupus contract kidney disease while others don’t, Dr. Putterman received a call from Dr. Jennifer Michaelson, a colleague and close friend. Dr. Michaelson had trained as a postdoctoral fellow in Dr. Barbara Birshtein’s laboratory at Einstein before moving to Boston to work for the pharmaceutical company Biogen Idec. Under the direction of Dr. Linda Burkly and Dr. Michaelson, the company was engaged in a lupus-relevant project to investigate the inflammatory effects of the newly identified TWEAK molecule. Biogen Idec had acquired a lupus strain it was going to use for some of its initial studies, called NZB X NZW F1, from the same commercial supplier that Dr. Putterman often used, but there was a problem: the mice, though prone to developing lupus, had remained stubbornly healthy. 

Chaim Putterman, MD

Dr. Putterman was invited to consult with Biogen Idec, and a trip to the company’s facilities in Cambridge revealed a likely reason for this puzzling inability of the NZB X NZW F1 mice to get sick: its gleaming, state-of-the-art animal facility where the mice were housed (“You could almost literally eat off the floor,” Dr. Putterman remarked) was too sterile to allow for severe disease to develop. An environmental component, in addition to the genetic component, presumably contributed to the inability of this particular strain to succumb to illness.

Dr. Putterman went on to establish a close collaboration with Biogen Idec scientists to uncover the role of the TWEAK molecule in lupus. Dr. Putterman and his co-workers discovered that that the TWEAK receptor (also known as Fn14) is present on certain kidney cells, and that treating these cells with TWEAK produces inflammatory substances that affect the kidneys. His next step involved moving from the test tube (“in vitro”) to the whole organism (“in vivo”). These in vivo studies received a major push from Biogen Idec’s development of normal and MRL/lpr lupus mice that were deficient for the Fn14 molecule from birth. Using a variety of mice with inflammatory kidney disease similar to lupus nephritis, Dr. Putterman showed that preventing the interaction of TWEAK with its receptor by genetic manipulation, or through administering a TWEAK-blocking antibody, resulted in significant protection from disease. These results, as well as studies in human lupus patients based upon the mouse experiments, opened the door for developing improved methods of monitoring patients, as well as possibilities for new treatments. 

Dr. Putterman is currently one of the investigators involved in an international, multicenter clinical trial testing the use of an anti-TWEAK antibody in addition to standard therapy to treat lupus-related kidney disease in SLE patients. The approval of this study (named ATLAS) by the appropriate U.S. governmental regulatory agency was supported by Dr. Putterman’s convincing experimental studies performed with his research collaborators at Biogen Idec. Sue Golding graduate students Sean Campbell and Hua-Xin Gao; Belfer Institute postdoctoral fellows Zeguo Zhao, Alberto Molano, Rahul Pawar, and Yumin Xia; and Montefiore physicians Noa Schwartz and Irene Blanco and research coordinator Nicole Jordan played a crucial role in these studies. 

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Contact Info

Division of Rheumatology
Albert Einstein College of Medicine
Jack and Pearl Resnick Campus
1300 Morris Park Avenue
Forchheimer Bldg., Rm 701N
Bronx, NY 10461

(718) 430-2078
Fax: (718) 430-8789


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