Lymphatic vessels act as communication highways, carrying signals from tissues to the immune system to alert it to infection, injury, or disease. When this system does not function properly, the body may struggle to fight infections, respond to vaccines, repair tissue, or control inflammation.

The new findings show that Langerhans cells play a key role during early life by helping lymphatic vessels grow and develop properly in the skin. This early “setup” has long-term consequences, influencing how well the immune system functions later in life.

“Our study shows that immune cells in the skin do much more than respond to threats—they help build the infrastructure the immune system depends on,” said senior author Theresa T. Lu, MD, PhD, who holds the St. Giles Chair for Research in the HSS Research Institute and is a member of Pediatric Rheumatology at HSS. “If this process is disrupted early in life, it can have lasting effects on immune health. Our results also underscore the critical role of skin health in regulating lymphatic vessel development and immune system function in health and disease.”

“These findings advance our understanding of how early-life biological processes influence long-term immune function,” explained JiHyun Sim, PhD, first author and Postdoctoral Fellow at HSS. “We are hoping to further understand if this physiologic process is disrupted to contribute to autoimmune disease.”

Key Findings

• Early-life development matters: Proper formation of lymphatic vessels in childhood is essential for strong immune responses in adulthood.
• New role for Langerhans cells: Beyond their known immune functions, these cells help guide the growth and programming of lymphatic vessels.
• Long-term impact: When Langerhans cells are reduced or impaired early in life, the immune system may be less effective later on.

Implications for Patients and Providers

The research suggests that conditions affecting skin health in early life—such as severe sunburn, burns, or certain autoimmune diseases like lupus—could interfere with Langerhans cells and, in turn, disrupt lymphatic development. This may contribute to weaker immune responses later in life, including reduced effectiveness of vaccines, increased susceptibility to infections, impaired healing, and potential autoimmune complications.

“These findings highlight the importance of protecting skin health early in life,” said Dr. Lu. “They also open the door to new approaches that could strengthen immune function by targeting the lymphatic system.”

A New Way of Thinking About Immune Health

The study adds to a growing body of evidence showing that early-life health and environmental factors can shape disease risk in adulthood. It also identifies a previously unknown mechanism by which immune cells influence tissue development—not just immune activation.

By uncovering how Langerhans cells regulate lymphatic vessel growth, researchers hope to pave the way for future strategies to improve immune responses and prevent disease across the lifespan.

Authors: JiHyun Sim, PhD, Richard Bell, PhD, Yurii Chinenov, PhD, Zhonghui Feng, PhD, Susan Chyou, BA, William D. Shipman, MD, PhD, Lionel Ivashkiv, MD, Theresa T. Lu, MD, PhD

Developing SR-878, a novel monoclonal antibody drug candidate targeting inflammation

SR-878, which builds upon foundational basic research discoveries made in the lab of Carl P. Blobel, MD, PhD, director of the Arthritis and Tissue Degeneration Program at the HSS Research Institute, is a monoclonal antibody drug candidate that targets inflammation in a new way.  More specifically, SR-878 targets a complex consisting of inactive Rhomboid 2 (iRhom2) and TACE/ADAM17 (ADAM17), a “master switch” for regulating the inflammatory response that is overactive in many autoimmune diseases.

ADAM17 is an enzyme involved in accelerating the body’s immune response, which has long held the interest of researchers due to its close association with an already proven target in the treatment of rheumatoid arthritis and other inflammatory diseases, the molecule TNF-alpha.

Researchers hypothesized that going after ADAM17 could prove even more effective than targeting TNF-alpha alone. “Beginning in the late 90s, there was an interest in targeting ADAM17 as another way to reduce TNF-alpha,” Dr. Blobel explains, “but it turns out, on its own, it wasn’t an optimal target because ADAM17 holds other important functions — such as protecting the skin and intestinal barrier.”

However, studies at HSS have since revealed that ADAM17 is regulated by its binding partner iRhom2. When iRhom2 is inactivated, those studies have demonstrated that the related iRhom1 can still protect against the problems observed when ADAM17 is blocked.  This research suggested that iRhom2 could be a safer and more effective target for drugs than ADAM17.

Collaborations with HSS rheumatologist Jane E. Salmon, MD, HSS Chief Scientific Officer Lionel B. Ivashkiv, MD, and HSS Physician-in-Chief Emerita Mary K. (Peggy) Crow, MD further supported this notion.  Those studies explored the effects of knocking out iRhom2 in preclinical mouse models with inflammatory arthritis as well as an autoimmune kidney disease called lupus glomerulonephritis. Their research demonstrated that the mouse models were protected from disease by blocking the TNF-alpha pathway and, in the case of lupus glomerulonephritis, also by inhibiting another pathway that contributes to inflammation, called the EGFR pathway. “We eventually realized that iRhom2 could be a very exciting target,” Dr. Blobel says.

The development of SR-878 underscores the importance of doing basic science research at academic institutions like HSS,” says Michael P. Ast, MD, orthopedic surgeon and Chief Medical Innovation Officer at HSS. “Scientific breakthroughs uncovered in the lab can be used to shape further studies that advance our understanding of complex diseases. Through the knowledge and expertise of investigators at HSS and SciRhom, we can build on the insights made together to ultimately benefit patients worldwide.”

Co-Founding & Advancing SciRhom

During a visiting professorship in 2015 in Munich, Germany, Dr. Blobel met two researchers, Drs. Jens Ruhe and Matthias Schneider, who have extensive experience in preclinical development of early to clinical stage antibody projects.

Together, HSS, the three researchers, and other experienced biotech entrepreneurs and investors, co-founded SciRhom in 2016 to translate Dr. Blobel’s scientific findings into novel therapies for autoimmune diseases.

Proof of concept studies performed by HSS scientist Gisela Weskamp, PhD, have since strongly supported the notions that targeting iRhom2 with SR-878 in a preclinical model of inflammatory arthritis is more effective than targeting TNF-alpha alone and is at least as effective as blocking both TNF-alpha and the EGFR pathway together. In addition, treatment with SR-878 also has potential to block another target of existing therapies, the interleukin-6 receptor. “We anticipate that SR-878 will simultaneously block multiple disease-causing pathways and therefore has potential for superior efficacy relative to current monotherapies,” she adds.

Following on the footsteps of its pre-clinical findings, SciRhom has since expanded its board and management ranks with former executives from the global pharmaceutical industry, including Chief Executive Officer Dr. Jan Poth, former Therapeutic Area Head Immunology at Boehringer Ingelheim, and board member Dr. Wolfgang Baiker, former CEO of Boehringer Ingelheim USA.

“SciRhom’s recent Series A financing and its approval to start clinical trials are pivotal milestones in the company’s journey towards commercialization” says Vijay Nair, Managing Director at the HSS Innovation Institute. “Bringing a discovery from the lab to patients requires immense dedication and collaboration across HSS and with the biotech entrepreneurial and investment communities. Their leadership and external validation have been critical in launching the company, securing funding, attracting world-class talent, pursuing pre-clinical development, and reaching this inflection point.”

“There is a lot of enthusiasm for this approach among members of the medical and investment communities. We are tremendously excited that we can now advance the study of this drug to human trials,” says Dr. Blobel.

The study published August 29 in Nature Communications shows that artificial intelligence and machine learning technologies can effectively and efficiently subtype pathology samples from patients with RA.

For this study, Dr. Richard Bell, an Instructor in the HSS Research Institute and Arthritis and Tissue Degeneration Program, and Lionel B. Ivashkiv,  MD, Chief Scientific Officer at HSS teamed up with  Dr. Fei Wang, a professor of population health sciences and the founding director of the Institute of AI for Digital Health (AIDH) in the Department of Population Health Sciences at Weill Cornell Medicine. 

“Our study addresses the analytical bottleneck of pathology research,” Dr. Bell said. “It is very time-consuming and tedious.” “Our tool automates the analysis of pathology slides, which may one day lead to more precise and efficient disease diagnosis and personalized treatment for RA,” said Dr. Wang. “It shows that machine learning can potentially transform pathological assessment of many diseases.”

There are several existing machine learning tools for automatic analysis of pathology slides in oncology. Dr. Wang and his colleagues have been working to expand the use of this technology in other clinical specialties.

Digital Pathology and Precision Medicine in RA

Distinguishing between the three subtypes of RA may help clinicians choose which therapy is most likely to be effective for a particular patient. This personalized medicine approach would represent a breakthrough in the care of patients with RA, and is a major goal of the Research Institute and Division of Rheumatology at HSS, which involves multiple laboratory and clinical investigators. “It’s the first step towards more personalized RA care,” Dr. Bell said. “If you can build an algorithm that identifies a patient’s subtype, you’ll be able to get patients the treatments they need more quickly.”

 The technology may provide new insights into the disease by detecting unexpected tissue changes that humans might miss. By saving pathologists time on subtyping, the tool may also decrease the cost and increase the efficiency of clinical trials testing treatments for patients with different subtypes of RA. “This work represents an important advance in analyzing RA tissues that can be applied for the benefit of patients” Dr. Ivashkiv said.

 Pathologists currently manually classify arthritis subtypes using a rubric to identify cell and tissue characteristics in biopsy samples from human patients—a slow process that adds to the cost of research and may lead to inconsistencies between pathologists.

 The team first trained its algorithm on RA samples from one set of preclinical models, optimizing its ability to distinguish tissue and cell types in the sample and sort them by subtype. They validated the tool on a second set of samples. The tool also yielded new insights into treatment effects in the models, such as reduced cartilage degradation within six weeks of administering commonly used RA treatments.

Then, they deployed the tool on patient biopsy samples from the NIH-supported Accelerating Medicines Partnership Rheumatoid Arthritis research consortium, of which HSS is a major participating site in research led by Laura Donlin, PhD, scientist and co-director of the HSS Precision Medicine Program and rheumatologist Susan  M. Goodman, MD. The new digital pathology approach could effectively and efficiently type human clinical samples. The researchers are now validating the tool with additional patient samples and determining the best way to incorporate this new tool into pathologists’ workflows.

 The team is working to develop similar tools for evaluating osteoarthritis, disc degeneration and tendinopathy.

The research reported in this story was supported in part by the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Institute of Allergy and Infectious Diseases, the National Institute of General Medical Sciences, and the National Institute on Aging, all part of the National Institutes of Health, through grant numbers R21AR071670, R01AI175212, UH2AR067690, UC2AR081025, F30AG076326, T32GM007356, AR046713, AR050401, R01AR078268, UC2AR081025, UL1TR001866 and R01AR056702.

Building on its established leadership in functional genomics research in autoimmune and musculoskeletal conditions, the aims of the next phase of the Rosensweig Center are to elevate precision medicine efforts through the application of “big data” approaches, explore how the dysregulation of certain immune cells drives autoimmune diseases, and understand how immune cells regulate musculoskeletal stem cell function—an emerging field known as immunoregeneration.

The overarching goals of this research are to enhance patient mobility and decrease pain by increasing clinicians’ ability to predict the best treatments for individual patients, and to discover transformative new therapies through enhanced understanding of disease mechanisms and modulating immune musculoskeletal cell crosstalk. The Rosensweig Center will continue to focus on diseases that are major causes of pain and disability in which HSS has a unique combination of clinical and research expertise: rheumatoid arthritis, scleroderma, lupus, osteoarthritis, and anterior cruciate ligament injury, as well as the pathological bone loss that occurs in osteoporosis, arthritis, and orthopedic implant loosening.

“We are honored to receive this extraordinary grant from The Tow Foundation to build upon our unparalleled knowledge, and extensive data sets and patient populations to conduct transformational new research with high impact and potential for translation to improved patient care,” said Lionel B. Ivashkiv, MD, Chief Scientific Officer and Director of the Rosensweig Center. “The expanded Rosensweig Center will harness HSS’s unique strengths by bringing together world-class scientists in the typically distinct areas of immunology and musculoskeletal biology, and by leveraging our genomics expertise together with the expertise of our collaborators in data analytics, AI/machine learning, advanced genomics technologies, and stem cell biology.”

“We’ve been incredibly impressed by the progress that Dr. Ivashkiv and his team have made in advancing cutting-edge genomics research since we first began our partnership over a decade ago,” said Emily Tow, President of The Foundation.  “We are pleased and proud to support the Rosensweig Center’s evolution as they continue to lead genomics research aimed at improving lives and are pleased that we can honor our dear friend David’s memory through this gift.”

“Orthopedic and rheumatologic conditions are the world’s leading cause of disability worldwide, and HSS has a special responsibility and opportunity to relieve their burden on people, businesses, and society as a whole,” said Bryan T. Kelly, MD, MBA, HSS President and CEO and Surgeon-in-Chief Emeritus.

“We are deeply grateful to The Tow Foundation for its incredible continued partnership as Dr. Ivashkiv and the Rosensweig Center team work to pioneer genomics research to accelerate the discovery of new treatment options to preserve the mobility and quality of life of patients here and across the globe.”

About The Tow Foundation

The Tow Foundation was established in 1988 by Leonard and Claire Tow as a way to give back to the communities that shaped them. Its five primary impact areas are equity and justice, medicine and public health, arts and culture, higher education, and civic engagement. Grounded in its decades of work in Connecticut and New York and based in New Canaan, CT, the foundation supports visionary leaders and nonprofit organizations to find and enact innovative solutions to persistent inequality. It works to ensure people can become full participants in their communities, achieve transformative and lasting progress, and develop approaches that allow everyone to reach their full potential. 

By partnering program scholars with HSS’s world-class researchers as mentors, students are able to experience biomedical research and understand that this is also a career option for them. “While many students beginning college are understandably excited about becoming a doctor and helping patients, fewer understand that you can also make a difference through a career in biomedical research,” said Dr. Theresa Lu, scientific director of the HSS Macaulay Scholars Program. “It’s our privilege to open the doors of discovery to these exceptional students and we hope to ignite a lifelong commitment to advancing musculoskeletal health and biomedical science.”

HSS's unparalleled expertise in the field of musculoskeletal health provide students the opportunity to explore the intersection of medicine and science in a cutting edge environment, and scholars could witness firsthand how research drives advancements across a spectrum of medicine.

The selected students, from the prestigious Macaulay Honors College, were each paired with an established investigator and their group members to serve as their research mentors. Additionally, each student was provided with a stipend to support them throughout this eight-week program. The organizing committee was comprised of Dr. Lu along with HSS CSO Dr. Lionel Ivashkiv, Vice President of Research Rosemarie Gagliardi, Director of Research Institute Operations Nicole Seate-Martin, faculty member Dr. Alexis Sideris, Tri-Institutional MD-PhD student Stephanie Azzopardi, and Weill Cornell medical student Branden Sosa. Dr. Sideris and Stephanie Azzopardi are former Macaulay Honors College students themselves, and Branden Sosa graduated from CUNY’s Hunter College.

HSS remains committed to fostering lasting connections with these gifted scholars and they look forward to witnessing their development as scientists. The next Macaulay Scholars Program is slated to begin this upcoming academic year. Prospective scholars are encouraged to apply.

This funding will support Dr. Dahia’s Spine Development and Regeneration Lab to study the potential of two important developmental molecules in the reversal of age-related intervertebral disc (IVD) pathologies and in the treatment of chronic back pain.

“Approximately 70 percent of the U.S. population is affected by chronic back pain, negatively impacting longevity and quality of life,” said Dr. Dahia. “There is currently no treatment available for disc degeneration, which is a big concern when you look at the world’s aging population. With the lack of treatment options, people can become dependent on strong pain relievers such as opioids.”

“It is an incredible honor for Dr. Dahia to receive these two NIH grants,” said Lionel B. Ivashkiv, MD, chief scientific officer at HSS. “Being awarded an NIH grant is the highest metric of scientific quality and impact. The application itself is peer-reviewed and quite rigorous.”

Dr. Dahia received the first 5-year grant for $2.8 million from the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)/NIH R01 to study the role of the sonic hedgehog (SHH)/Brachyury axis in the maintenance of the postnatal IVD. This work aims to identify the role of Brachyury, a critical developmental molecule first reported in the nucleus pulposus cells of postnatal disc by Dr. Dahia herself in 2009, in the growth and maintenance of the postnatal IVD, how its age-related loss causes disc pathologies and peripheral sensitization and pain, and whether this can be prevented. The study findings will also identify targets to reverse painful disc pathology and help regenerate the disc.

She was then awarded the National Institute of Aging (NIA)/NIH R01 5-year grant for $3.3 million to study the role of developmental signaling pathways in the maintenance of spinal discs. The study is focused on understanding the crosstalk between major developmental signaling pathways interacting with SHH signaling (also first shown by Dr. Dahia in 2009) in temporal regulation of the different components of the IVD and their beneficial effect in maintenance and activation of disc progenitor cells. The research intends to discover if there is a potential for disc regeneration using its own cells, and is being done in collaboration with Todd J. Albert, MD, spine surgeon and surgeon-in-chief emeritus of HSS. Dr. Albert and his team will test Dr. Dahia’s findings in clinical conditions.

“Initially, we found that these crucial developmental molecules are expressed in very young spinal discs, and recently we observed that they decline with age and disc pathology, hence we are now evaluating their function from stages of growth and maturation to aging,” explained Dr. Dahia.

Dr. Dahia has committed her career to developing a full understanding of disc biology as they grow, mature, and age to identify potential avenues for therapeutics. She previously received an NIH grant in 2014 to study how the Wnt/SHH signaling loop controls IVD growth and differentiation. When Dr. Dahia began her research in disc biology over a decade ago, she was one of the first to study the beneficial role of developing molecules in the postnatal spine. Now, this is being adapted in other musculoskeletal research in a broader sense.

According to Dr. Dahia, other researchers have tried to use stem cells to solve these issues, but the cells are unable to survive due to the harsh microenvironment of the disc. “Our lab’s process is unique, as we aim understand the cellular and molecular basis of disc pathology and know how to intersect it, using our unique and novel genetic strategies,” she noted.

Dr. Dahia’s Spine Development and Regeneration Lab at HSS concentrates on understanding the role of key developmental cell signaling pathways and molecules in the development and homeostasis of various musculoskeletal tissues including the IVD, spinal column, growth plate, and tendon. The lab’s primary focus is on IVD development and maintenance and whether developmental pathways and molecules can prevent age-related disc pathologies and associated neurological symptoms or regenerate the degenerated discs.

“These scientific discoveries can directly impact future directions of musculoskeletal research to best improve clinical outcomes,” said Dr. Dahia who noted that HSS research is aimed at enriching the lives of patients suffering from debilitating orthopedic and rheumatic conditions.

HSS is the world’s largest academic medical center specialized in musculoskeletal health, spanning orthopedics, rheumatology and related disciplines. The HSS Research Institute maintains 20 laboratories dedicated to solving debilitating orthopedic and rheumatic conditions such as arthritis, bone and soft tissue injuries, autoimmune diseases, and musculoskeletal pain and deformities. There, more than 300 dedicated personnel focus on tissue repair, improving surgical outcomes, autoimmunity and inflammation, genomics, new treatments, and precision medicine.

“HSS has a long history of contributing to the collective base of clinical and basic science knowledge and finding healthcare solutions for complex conditions,” said Louis A. Shapiro, President and CEO, HSS. “We’re proud that through the joint efforts of our institution and philanthropic support, we will have the ability to make a strong impact on this growing and vital area of research.”

“As experts in inflammatory disorders and in the development of interventions for overactive immune responses, the clinicians and researchers at HSS are well-positioned to investigate many of the adverse effects of COVID-19,” says Lionel B. Ivashkiv, MD, Chief Scientific Officer at the HSS Research Institute. “This includes studying the causes of these adverse effects as well as how to prevent and treat them.”What follows are descriptions of the first group of funded projects in basic/translational research:

Activation of pDCs by SARS-CoV-2 and Its Impact on Macrophage Response

Principal Investigator: Franck Barrat, PhD

Co-Investigator: Marie-Dominique Ah Kioon, PhD

This project will study cell types that are responsible for cytokine storm syndrome — the hyperactive immune response seen in people with COVID-19 — by looking at how certain immune cells are activated by SARS-CoV-2. Research in mice infected with SARS-CoV, a coronavirus similar to the one that causes COVID-19, has suggested that plasmacytoid dendritic cell precursors (pDCs) are key to the immune response to infection. These pDCs activate macrophages, which in turn secrete cytokines. In the SARS-CoV research, depletion of pDCs appeared to protect the mice from lethal lung injury. Using blood samples from donors, the investigators will study the pathway by which pDCs activate macrophages and look at ways to therapeutically block that process.

Inhibiting RNA Polymerase II Transcription Complexes in Macrophages to Target COVID-19–Associated Cytokine Storm

Principal Investigator: Inez Rogatsky, PhD

Co-Investigators: Steven Josefowicz, PhD, and Robert P. Fisher, MD, PhD

This pilot project will dissect the role of macrophages in SARS-CoV-2-induced acute respiratory distress syndrome (ARDS), the main driver of COVID-19-associated mortality. We will test small-molecule inhibitors of RNA Polymerase II (Pol II) transcription complexes for their ability to modulate type I interferon and inflammatory pathways in monocytes/macrophages. This research will be done using cultured macrophages as well as donor blood and blood from COVID-19 patients.

Mechanisms of Cytokine Storm in Patients with COVID-19

Principal Investigator: Mary K. Crow, MD

Co-Investigators: Mikhail Olferiev, MD, and Lionel B. Ivashkiv, MD

The objectives of this study are to describe the process of the cytokine storm in people with COVID-19 and to identify biologic predictors of a favorable outcome in patients with severe cases of the disease. The project aims to characterize immune cell populations seen in COVID-19 patients who experience cytokine storm and compare them to those patients who do not, to compare the immune response before and after patients are given the anti-inflammatory drug anakinra, and to identify measures that suggest patients are more likely to decline and eventually require mechanical ventilation. The research will employ blood samples from HSS patients who are being treated for COVID-19 at New York–Presbyterian Hospital and who meet certain other qualifications.

What follows are descriptions of the first group of funded projects in the areas of clinical and health outcomes research:

Response to and Recovery from TKA in Patients with Antibodies to SARS-CoV-2

Principal Investigator: Miguel Otero, PhD

Co-Investigators: Meghan Kirksey, MD, PhD, and Peter K. Sculco, MD

It is unknown if people who have been exposed to COVID-19 may be at higher risk of experiencing an abnormal immune response following surgery, resulting in poor outcomes. This study will evaluate the response to and recovery from total knee arthroplasty (TKA) in people who have antibodies to COVID-19 — a marker of exposure. This study will include both patients who have COVID-19 antibodies and those who don’t, to act as controls. Patients will be followed for six weeks after surgery and evaluated for the presence of certain immune markers in the blood, as well as symptoms of inflammation including pain and stiffness in the joint.

SARS-CoV-2 Exposure and the Role of Vitamin D Among Hospital Employees

Principal Investigator: Emily M. Stein, MD, MS

Co-Investigators: Theresa T. Lu, MD, PhD; Andy O. Miller, MD; Jeri Nieves, PhD; and Alana Serota, MD

It is unknown if people with vitamin D deficiency may be more likely to become infected with COVID-19. This study will investigate vitamin D status and associated immune markers as risk factors for COVID-19 infection in a cohort of healthcare workers. Healthcare workers are at higher risk of contracting COVID-19 than the general population, making them a good group to study. Vitamin D is critical for immune function and is known to be protective against respiratory-tract infection and tuberculosis. This prospective, observational study will follow healthcare workers at HSS and at other healthcare facilities for one year, to determine whether levels of vitamin D and certain immune cells in the blood make someone more susceptible to COVID-19 infection.

Association of Immunomodulatory Medication Use and Social Determinants of Health with COVID-19 Infection in Systemic Rheumatic Disease Patients in New York City

Principal Investigator: Medha Barbhaiya, MD, MPH

Co-Investigators from HSS: Lisa Mandl, MD, MPH; Catherine MacLean, MD, PhD; Vinicius Antao, MD, PhD; Jane Salmon, MD; and Mayu Sasaki, MPH

Other Co-Investigators: Candace Feldman, MD, MPH (of Brigham and Women’s Hospital); Debra D’Angelo, MS (of Weill Cornell Medicine)

Using data from the INSIGHT Clinical Research Network, a central repository containing longitudinal electronic health data for residents of New York City, investigators will assemble a cohort of patients being treated with immunomodulatory medications for rheumatic disease. This patient population will then be used to study the effect of these medications on COVID-19 incidence and outcomes. Retrospective data will be used to evaluate the incidence and severity of COVID-19 in these patients. Patients will also be studied prospectively to determine whether there’s a relationship between COVID-19 infection and future rheumatic disease as well as to study connections between infection and future psycho-social issues.

Assessment of Surgical Outcomes in the COVID-19 Pandemic Era

Principal Investigator: Andy O. Miller, MD

Co-Investigators: Scott A. Rodeo, MD, and Mark Fontana, PhD

Investigators will implement a patient registry to evaluate how COVID-19 affects outcomes and complication rates after orthopedic surgery. This registry, along with COVID-19 screening procedures, will provide the tools to address specific research questions. Among these questions are determining the incidence of current and prior infection among the HSS surgical population, the clinical features associated with current and prior infections in this patient population, and whether COVID-19 status affects short-term complication rates.

What follows is a description of an integrated multidisciplinary study being undertaken jointly by the Adult Reconstruction and Joint Replacement (ARJR) Perioperative Research Group, Anesthesiology and Rheumatology:

Prediction and Prevention of Postoperative Blood Clots in COVID-19 Patients

Principal Investigators: Friedrich Boettner, MD; Kethy M. Jules-Elysee, MD; Lisa A. Mandl, MD, MPH

Co-Investigators: ARJR surgeons: Alejandro Gonzalez Della Valle, MD; Jason Blevins, MD; David J. Mayman, MD; Peter K. Sculco, MD; Geoffrey H. Westrich, MD and Thomas P. Sculco, MD

Medicine/Rheumatology: Medha Barbhaiya, MD, MPH; Doruk Erkan, MD, MPH; Deanna Jannat-Khah, DrPH

Pathology: Thomas W. Bauer, MD, PhD

Anesthesiology: Stavros G. Memtsoudis, MD, PhD, MBA; Alexandra Sideris, PhD

ARJR: Amethia Joseph, MHA; Ethan Krell, MS

Weill Cornell Medicine: Raymond David Pastore, MD

Recent literature suggests that one of the major complications seen in people with COVID-19 is thrombosis (the formation of blood clots) due to endothelial dysfunction, persistent inflammation and potentially antiphospholipid antibodies. As elective surgeries resume, those with prior exposure to SARS-CoV-2 will inevitably present for treatment, and some may have perioperative management considerations related to their risk of deep-vein thrombosis. This project will use, a noninvasive device that can determine clotting risks, to investigate whether people who have had COVID-19 have a more dysfunctional endothelium preoperatively and at 24 hours after surgery. The investigators will measure antiphospholipid antibodies and inflammatory markers, and evaluate the prevalence of asymptomatic post-operative deep-vein thrombosis in people who undergo TKR and have SARS-CoV-2 antibodies.

COVID-19 Translational Research Core at HSS

Principal Investigator: Theresa Lu, MD, PhD

Co-Investigators: Jessica Andrés-Bergós, PhD; Miguel Otero, PhD and Emily M. Stein, MD, MS

The COVID-19 Translational Research Core (TRC) was designed to fill critical gaps in the resources needed to promote the broad range of COVID-19–related clinical and translational research at HSS. The TRC will provide consultation on the design and implementation of COVID-19 research in the areas of orthopedics, rheumatology and metabolic bone disease; support for a COVID-19 biobank; and technical expertise and facilities required for clinical and translational researchers working on COVID-19–related projects. The TRC staff will help to acquire, house, and track biospecimens from investigator-initiated COVID-19–related research studies.

Today, HSS announced that The Tow Foundation pledged an additional $5.6 million to transform the Center’s impact by highlighting translational research and expanding its focus from autoimmune disease to more broadly address the major musculoskeletal conditions which are seen every day at HSS. The goals of this new work are to prevent and repair musculoskeletal tissue damage related to acute or chronic injury, aging, and autoimmunity and inflammation.

"We are honored to receive this extraordinary grant from The Tow Foundation to build upon and leverage our expertise in genomics to ultimately improve patient outcomes in musculoskeletal care," said Lionel Ivashkiv, MD, chief scientific officer and director of the Rosensweig Center and HSS Research Institute. "HSS is uniquely positioned to study innovative solutions to prevent and repair tissue damage by bringing together world-class scientists with clinicians to pioneer applications in new disease areas."

"Musculoskeletal conditions affect 127 million adults in the United States and account for $874 billion, or 6 percent of national GDP, in direct and indirect costs," said Louis A. Shapiro, president and CEO at HSS. "There is a need now more than ever for research to preserve mobility."

"As an institution, we are committed to translational research in order to accelerate the discovery of new treatment options for patients here and across the globe," added Mr. Shapiro.

Specifically, the researchers will look at preserving mobility and function by repairing and rejuvenating tissues in these areas: tissue damage in autoimmune diseases; joint damage in arthritis; tendon degeneration and associated muscle weakness in tendinopathy; and bone loss in osteoporosis, arthritis and orthopaedic implant loosening. Scientists will work on developing therapies to promote repair of tissues after injuries and after surgeries such as joint replacement and spine fusion.

"These are areas that represent the major causes of pain and disability in our HSS patient population," said Dr. Ivashkiv. "Genomic approaches have been minimally used in some of these fields of study, so we are poised to perform transformative research."

"This is an exciting time to be applying genomics to tissue repair," explained Dr. Ivashkiv. "Recent scientific advances have provided new insights into the mechanisms of tissue repair that can be used to develop new therapeutic approaches."

"By the end of this grant, we hope to achieve successful application of precision medicine approaches to predict prognosis and response to therapy," added Dr. Ivashkiv. "Additionally, we would like to test new therapies in pre-clinical models and develop partnerships with the HSS Innovation Institute and others for translation to patients."

Under the leadership of Dr. Ivashkiv, the Center has already made important contributions to understanding the function of autoimmunity genes and molecular pathways in conditions such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and scleroderma.

It has also recruited and mentored junior faculty who have obtained NIH grants, which is the highest metric of scientific quality and impact.

The Center will be expanding to 13 HSS faculty and will continue collaborations with investigators at Weill Cornell Medicine, Sloan-Kettering Institute and the New York Genome Center (NYGC).

About The Tow Foundation
Established in 1988 by Leonard and Claire Tow, The Tow Foundation funds projects that offer transformative experiences to individuals and create collaborative ventures in fields where they see opportunities for breakthroughs, reform, and benefits for underserved populations. Investments focus on the support of innovative programs and system reform in the areas of juvenile and criminal justice, groundbreaking medical research, higher education, and cultural institutions. For more information, visit http://www.towfoundation.org.