Thirteen scientists across the U.S. were awarded arthritis research grants, giving hope to all who are suffering.
All grant applications are carefully reviewed by ANRF’s world-renowned Scientific Advisory Board (SAB). The SAB only chooses the best and brightest emerging arthritis research scientists with the most innovative and cutting edge projects.
Below are this arthritis research scientists and a brief summary of their work:
Shahla Abdollahi-Roodsaz, PhD
New York University School of Medicine
New York, NY
Trillions of harmless bacteria inhabit human intestines and live in harmony with their host. The totality of these microbes and their genes, called the microbiome, affects many aspects of a healthy life. Among others, the microbiome shapes our immune system and can therefore play an important role in autoimmune diseases such as rheumatoid arthritis (RA). Evidence suggests that specific types of intestinal bacteria are increased in patients recently diagnosed with RA.
Dr. Abdollahi-Roodsaz will investigate the direct influence of these RA-associated bacteria on the appearance of arthritis in animal models. This will clarify whether these bacteria in fact have a function in causing disease and will extend our understanding of the mechanisms linking the intestinal microbiome with the pathogenesis of arthritis. With this knowledge we may develop novel therapies targeted at specific microorganisms, their identifying receptors, and the cell types that mediate disease. Further, these insights may also shed light on other autoimmune inflammatory diseases associated with alterations in the microbiome.
Pallavi Bhattaram, PhD
Rheumatoid arthritis is a common joint disease causing distress and disability in large percentage of adults. Abnormal changes in specialized cells lining the joint surfaces, known as the fibroblasts-like synoviocytes, is one of the major causes of this disease. In healthy joints, fibroblasts-like synoviocytes are critical for the maintenance of joint integrity. They produce molecules that lubricate joints and help to protect the joints from wear and tear. However, during rheumatoid arthritis, these specialized cells transform into cancer-like cells. They increase in numbers and act as a source of molecules that destroy the joints.
Despite this knowledge, incomplete understanding of the genes and pathways that regulate fibroblasts-like synoviocytes has limited the development treatment strategies that can target these cells. This study focuses on uncovering the roles of a group of genes that transform the healthy joint protecting cells into joint destroying cells. This knowledge could be used develop treatments that limit the joint damage in rheumatoid arthritis.
Nidhi Bhutani, PhD
Osteoarthritis (OA) is the most common form of arthritis that affects approximately 27 million people in America. Current treatments are limited to pain management. OA is marked by joint cartilage degeneration. Dr. Bhutani’s recent studies have identified that normal and OA cartilage cells from patients differ greatly in the function of a novel family of enzymes. These enzymes are responsible for modifying the DNA of OA genes; therefore, these enzymes may be central regulators of gene expression changes in OA.
Dr. Bhutani’s second year study will identify the genes that are regulated by these enzymes in normal and OA cartilage to understand the particular enzyme’s affect on the initiation and progression of OA. These experiments will show how accumulated environmental changes such as injury, aging or obesity can affect activity of enzymes. Dr. Bhutani will then evaluate if targeting this enzyme and its targets may be therapeutic in early or late stage OA.
Susan Carpenter, PhD
University of California, Santa Cruz
Santa Cruz, CA
While acute inflammation is mostly beneficial, unchecked or dysregulated inflammation can have devastating consequences leading to a wide range of diseases including Rheumatoid Arthritis, Systemic Lupus Erythematous (lupus) and Cancer. Thus, given the significance of these devastating diseases, new approaches towards understanding pathology and gene mechanism are urgently needed.
It has been over a decade since the human genome was sequenced. Since then there has been huge improvements in our ability to carry out sequencing. The classical understanding of the genome was that DNA is transcribed into RNA, which makes proteins that carry out various biological functions. However sequencing studies have shown that only a small portion (2%) of the genome results in protein, yet there are very large amounts of RNA being produced (85% of the genome). The major class of RNA molecules produced from the genome are called long noncoding RNA (lncRNA). Dr. Carpenter’s project aims to understand how a specific lincRNA is involved in the pathogenesis of inflammatory arthritis. Obtaining a better understanding of the role of lncRNA in inflammatory conditions could lead to the development of new biomarkers for disease and unveil new therapeutic targets.
Iouri Chepelev, PhD
Cincinnati Children’s Medical Center
Co-Funded Grant with National Psoriasis Foundation
ANRF and the National Psoriasis Foundation (NPF), based in Portland, OR have awarded Dr. Chepelev a two-year, $200,000 grant to study the causes of psoriatic arthritis. Dr. Chepelev is studying how specific genes relate to the causes of arthritis and psoriasis. Psoriatic arthritis is a debilitating autoimmune inflammatory disease involving the skin and joints.
For the first time anywhere, Dr. Chepelev will lead a team of experts at Cincinnati Children’s who will measure activity levels of long stretches of DNA to see if certain genes cause psoriatic arthritis. The study will shed new light on gene-regulatory mechanisms involved in psoriatic arthritis.
ANRF often co-funds scientific research with other national arthritis charities to further our mission of curing arthritis through research.
Jenna Galloway, PhD
Massachusetts General Hospital
Osteoarthritis is a complex disease resulting in inflammation and deterioration of cartilage and ligaments in the joint. Currently, the treatment options for these injuries are limited, and lasting repair of the tissue is a considerable challenge. Factors that prevent or reverse degeneration or improve joint tissues would be ideal candidates for new therapeutic treatments for patients.
Recently, the use of transgenic zebrafish for cell based screening assays has identified small molecules with potent activity in mouse and human cells. Dr. Galloway will use transgenic zebrafish lines to identify chemical compounds that promote tendon and cartilage growth then analyze the activity of these new drugs in human stem cell culture. Molecules with potent capabilities would be prioritized for future studies. Her goal is to use this unique screening strategy to identify new pathways with therapeutic potential for degenerating joint tissues.
J. Michelle Kahlenberg, M.D., Ph.D.
University of Michigan
Ann Arbor, MI
Systemic lupus erythematosus (SLE or lupus) is a severe autoimmune disorder that can adversely affect many organs, including the skin, kidney, blood and joints. Lupus is characterized by “flares” of increased disease activity that require treatment with aggressive immunosuppressive medications. Often, these flares can be predicted by the onset of a lupus skin rash. However, how this rash relates to systemic disease development remains unclear.
Dr. Kahlenberg has developed a model in which lupus-prone mice develop a rapid flare of kidney inflammation following skin injury. In year one, her team characterized how this was happening. For year two, they will block a specific inflammatory pathway that prevents the kidney inflammation and determine whether activation of this pathway in the skin or in the kidney is driving the inflammatory response. Dr. Kahlenberg will also determine whether blocking this pathway is able to reverse kidney inflammation once it is started.
She anticipates that this study will show skin inflammation as an important trigger for kidney inflammation in lupus. This work will potentially identify a specific, novel target for prevention or treatment of disease flares in lupus.
Gang Li, PhD
Brigham and Women’s Hospital
Complex diseases such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are associated with the effects of multiple genes in combination with lifestyles and environmental factors. They are difficult to study and treat because the specific factors that cause them have not yet been identified.
Genome-wide association study (GWAS) has identified numerous genetic variants that are associated with complex diseases by comparing DNA sequences from people with the disease and without. Dr. Li has developed two novel techniques to study the DNA sequencing enabling him to identify the to disease and to understand the mechanism that regulates the DNA expression in these diseases.
This project will identify the gene network associated with high risk of RA and JIA, with the goal of identifying novel targets for therapy and potentially, a more personalized approach to arthritis patient care.
Lori Broderick, MD, PhD
University of California, San Diego
San Diego, CA
Autoimmune disease is caused by a malfunctioning immune system. Dr. Broderick has identified a syndrome of immune deficiency, in which patients have inherited defects in the cells that protect us from infections, specifically B cells. In this syndrome, patients also have skeletal changes, which affect the use of their hands and feet.
Currently, much remains unknown about how B cells develop in humans. The primary goal of Dr. Broderick’s project is to understand how mutations in a single specific protein cause defects in the immune system as well as in the development of bones. By learning from patients with defined immune syndromes, we can better understand normal immune cell development, function and how these cells interact with each other.
Dr. Broderick plans to use this knowledge to design life altering diagnostic tests and identify new life saving therapies which can be applied to more common immune system defects, including autoimmunity driven by B cells.
Hilde Schjerven, PhD
University of California, San Francisco
San Francisco, CA
In autoimmune disease, the body’s immune system attacks healthy parts of the body as if they are foreign or damaged. It is not fully understood what determines the development of autoimmunity, but it is believed to be due to a combination of genetic predispositions (inherited susceptibility) and environmental factors.
Genome wide association studies (GWAS) are used to scan DNA to find markers for genes that can predispose for disease. Through such GWAS studies, it has recently been found that several autoimmune diseases, including lupus, are associated with a gene family called Ikaros.
Because autoimmunity is a complex disease that depends on multiple cell types and tissues within the body, mouse models are powerful tools to help understand and study this disease. Dr. Schjerven has created new Ikaros mutant mice that provide a powerful model to study the role of this gene in development of autoimmunity.
The insight gained from these studies will benefit the larger scientific community by shedding light on the general mechanisms of autoimmunity, and may lead to future development of targeted therapies for autoimmune disease in patients with genetic predisposition due to the Ikaros gene.
Shruti Sharma, PhD
University of Massachusetts Medical School
Osteoporosis is a progressive, age-related loss of bone, which dramatically reduces the quality of life. Osteoblasts (bone-building) and osteoclasts (bone-breaking) are the two cell types that normally coordinate the constant ‘remodeling’ of bone, so that bone density is perfectly maintained.
Increased inflammation is known to affect the normal activities of osteoblasts and osteoclasts, leading to changes in the bone architecture and density. A leading source of inflammation during disease comes from the body’s first line of defense or the ‘innate’ immune response, which detects initial damage or infection within the body. Pathways that promote innate inflammation are present within most cells of the body (including
osteoblasts and osteoclasts). However, if and how innate inflammation pathways within
osteoblasts and osteoclasts contribute to osteoporosis has never been tested.
Insights into the initial events that drive the innate immune inflammation during osteoporosis would provide vital therapeutic targets and will have broad applicability to other age-related and autoimmune diseases. Dr. Sharma hopes to identify not only a new but key inflammatory pathway that is initiated in osteoblasts and reveal more effective targets for therapeutic intervention.
Stephanie Stanford, PhD
La Jolla Institute for Allergy and Immunology
San Diego, CA
Dr. Stanford’s objective is to reveal a novel mechanism of action of one of the most potent human arthritis genes, called PTPN22. When mutated in humans, this gene substantially contributes to risk of rheumatoid arthritis (RA), ranking as the second most significant RA risk gene. This project is focused on understanding how mutated PTPN22 can cause RA, with the goal of developing personalized ways to treat disease.
This project addresses the mechanism of one of the most powerful RA risk genes. By providing evidence that PTPN22 causes RA through deficient suppression of autoimmune-promoting cells, Dr. Stanford will uncover an important mechanism underlying RA. By clarifying the immunological pathways that promote disease in patients with this mutated gene, this project might help identify targets for personalized therapy for RA.
Wentian Yang, PhD
Brown University – Rhode Island Hospital
Current osteoarthritis (OA) treatment focuses on symptom relief but does not materially alter disease progression. OA prevention and treatment continue to be a clinical challenge due to the limited self-healing capacity of joint cartilage.
In Dr. Yang’s second year of his OA study, he is looking at the effect of certain genetic signaling to enhance and sustain cartilage formation in joints. Using a surgery-induced osteoarthritis mouse model, Dr. Yang is testing whether a specific gene’s deletion or reduction causes anti-degeneration, as well as regeneration of cartilage.
Dr. Yang’s work experiments will help elucidate this specific gene’s functions in cartilage and will lay a new foundation on which novel therapeutics could be developed to treat OA and other degenerative cartilage diseases.