IMRF + Yale University:
The IMRF is thrilled to annouce its recent grant to Dr. Wei Zhang at Yale University. Dr. Zhang’s project is focused on the following: Connective tissue disorders (CTDs) can arise from specific genetic mutations that adversely affect the primary components of the extracellular matrix (ECM), resulting in decreased mechanical strength of blood vessels, especially arteries, and leading to aneurysms, dissections, and ruptures. Cardiovascular events are major complications for patients with CTDs, who often require surgical interventions to prevent life-threatening complications. Effective vascular repair and replacement can significantly improve the survival rate. However, the primary challenge in patients with CTD is their fragile vascular walls, which have underdeveloped connective tissue, leading to poor surgical outcomes compared to patients without CTDs. Synthetic grafts used in these surgeries are generally less compliant and fail to match the mechanical properties of native vessels, increasing the risk of vascular injury and necessitating reinterventions. Our aim is to develop elastic tissue-engineered vascular grafts (TEVGs) using human induced pluripotent stem cell-derived vascular smooth muscle cells by enhancing the production and deposition of elastic fibers within these grafts. TEVGs with improved elasticity and compliance are expected to better accommodate the fragile vascular wall of patients with CTDs, thereby reducing the need for reinterventions.
IMRF + New York University: Update
The IMRF is pleased to share a recent press release posted by NYU regarding Dr. Cowman and her team’s research!
A link to the press release can be found here: https://engineering.nyu.edu/news/revolutionizing-cartilage-repair-role-macrophages-and-hyaluronic-acid-healing-injuries
IMRF + The Cleveland Clinic
The IMRF recently funded a research project under the direction of Dr. Suneel Apte at the Cleveland Clinic. Inherited connective tissue diseases can arise not only from mutations in structural proteins such as collagens in extracellular matrix (ECM), but also from mutations in helper proteins called matricellular proteins, which may assist in secretion, folding and assembly of ECM molecules. In addition to natural genetic conditions, the functions of helper proteins can be defined by analysis of genetically engineered mice with mutations in specific genes of interest. The Apte laboratory is currently investigating the impact of two such helper genes, Adamtsl1 and Adamtsl3. The proteins they encode, ADAMTSL1 and ADAMTSL3 are closely related and the genes are expressed in musculoskeletal tissues, skin and lungs. The laboratory will use diverse morphologic, cell biology and biochemical techniques to define the tissue defects in these mice and determine the previously unknown mechanisms of action of these proteins in relation to ECM.
IMRF + Columbia University: Dr. Xuebing Wu
The IMRF is excited to announce its support of Dr. Xuebing Wu’s research at Columbia University. Marfan syndrome is a genetic disorder that affects approximately 200,000 people in the United States each year. It affects the connective tissue between organs, and while symptoms can vary greatly, many Marfan patients experience disproportionate arms, legs and fingers; extreme nearsightedness and curvature of the spine; and in some instances, life-threatening abnormalities of the aorta. Though it is a heterogeneous genetic disorder, Marfan is closely associated with the gene FBN1. The long-term goal of Dr. Xuebing Wu is to develop a one-time, off-the-shelf gene editing therapy for Marfan patients with an FBN1 deficiency – something that may help 40% or more of those with this diagnosis. With the support of the Ines Mandl Research Foundation, Dr. Wu will be working toward such an intervention, testing the feasibility of rescuing FBN1 deficiency using vascular smooth muscle cells (vSMCs) derived from cells of Marfan patients. CRISPR – an acronym for ‘clustered regularly interspaced short palindromic repeats’ – is a technology developed to modify the DNA of living organisms. And while this technology is extraordinary, it is also expensive – developing a unique modification for each Marfan patient would be cost prohibitive, and an inefficient use of resources. Dr. Wu’s goal, then, is to develop an easily accessible, generally affordable intervention that may benefit a significant percentage of those with Marfan syndrome. He will be using CRISPR technology to address a large number of different FBN1 mutations in Marfan patients; preliminary data suggests that this may be an especially effective and efficient way to help these patients.
IMRF + Washington University in St. Louis
The IMRF is pleased to announce its support of Dr. Carmen Halabi’s research at Washington University in St. Louis. Dr. Halabi’s lab focuses on understanding how vascular elastic fibers, the rubber bands that allow blood vessels to withstand the pumping of the heart, develop and how abnormalities in their development lead to disease. Using a mouse model of cutis laxa, a connective tissue disorder characterized by skin and skeletal abnormalities, aortic aneurysms and pulmonary emphysema, her group determined that large vessels have different molecular requirements for elastic fiber assembly compared to small vessels. The goal of this funded project is to determine the contribution of two specific molecules, fibulin-5 and lysyl oxidase like 1, to elastic fiber assembly along the arterial tree. Using knock-out mouse models and state-of-the-art microscopy and physiology techniques, the studies will investigate the effect the loss of these two molecules has on large and small arteries both structurally and functionally. Understanding the molecular requirement for elastic fiber assembly along the arterial tree is a necessary first step for devising potential therapeutic strategies to treat diseases where elastin is either insufficiently made or abnormally assembled.
IMRF + Shaare Zedek Medical Center
The IMRF has recently funded a study on fat-derived stem cells for the treatment of knee osteoarthritis. This study, almost entirely funded by the IMRF, will evaluate the ability of stem cells found in the patients’ own fat to both relieve the pain of chronic arthritis and improve function. The study is under the leadership of Gershon Zinger MD MS and Racheli Sharon Gabbay PhD, and will be performed at Shaare Zedek Medical Center in Jerusalem. The procedure starts with a 20 mini-liposuction under local anesthesia. The fat is then processed using a sterile automated process and re-injected into the arthritic knee. Patients will be followed for one year after the procedure. Treating arthritis with our own stem cells is a paradigm shift. We have the ability to heal ourselves. The IMRF is pleased to fund this cutting-edge research.
IMRF + The Hebrew University of Jerusalem: Dr. David Naor
The IMRF is excited to announce it has funded a study on the therapeutic effect of 5-MER peptide (5-MP) on connective tissue diseases. With support of IMRF, Dr. Naor’s Lab collaborated with Prof Mary Cowman from NYU in a project showing that a 5-MER peptide (MTADV) alleviates the activity of mouse models of Rheumatoid Arthritis (RA), Crohn Disease/Ulcerative Colitis and Multiple Sclerosis, all of which are associated with pathology in connective tissues. Further, 5-MP inhibited the release of pro-inflammatory cytokines (IL-6, IL-β, TNFα) from SAA-stimulated synovium fibroblasts, derived from a human RA patients (Maayan Hemed-Shaked et al.,… David Naor , MTADV 5-MER peptide suppresses chronic inflammations as well as autoimmune pathologies and unveils a new potential target-Serum Amyloid A . J Autoimmun . 2021 Nov; 124:102713). In the continuation of this project, supported also by IMRF, Dr. Naor’s lab is exploring the mechanism of action of 5-MP therapeutic effect, using the mouse RA model of Collagen-induced Arthritis(CIA) and human fibroblasts, an important players in the Connective Tissue pathology. This last study is aimed 1) to strengthen our claim that SAA is a 5-MP target under in vivo conditions. 2) To determine the effect of 5-MP on bio-markers of arthritic mice. 3) To study the effect of 5-MP on components of the connective tissue. To this end we have already found that 5-MP inhibits human fibroblasts biological functions, such as SAA-induced cell proliferation (or cell growth). The fibroblasts generate matrix metalloproteinases (MMPs), which degrade collagen in RA patients, leading to the connective tissue disease. The inhibition of the fibroblasts proliferation by the peptide reduces their involvement in the connective tissue pathology.
IMRF + University of Health Sciences and Pharmacy and Washington University Medical School in St. Louis
The IMRF is pleased to announce it has funded a study on the biomechanical properties of zonular fibers under the direction of Dr. Juan Rodriguez of University of Health Sciences and Pharmacy in St. Louis and in collaboration with Dr. Steven Bassnett of Washington University School of Medicine in St. Louis. Zonular fibers are composed largely of fibrillin microfibrils, organized into micron-sized filaments that suspend the lens inside the vertebrate eye. The goal of the project is to determine how the biomechanical properties of these fibers emerge from microfibril interactions. Given the structural and biomechanical similarities between zonular fibers and elastin-rich elastic fibers, their findings may have broad relevance to connective tissue research.
IMRF + New York University: Update
The IMRF is excited to share that NYU posted an article about Dr. Cowman’s research, which has just been published in a major scientific journal. A link to the article can be found here: Biomedical engineers show potential of new peptide for fighting Alzheimer’s disease and COVID-19 | NYU Tandon School of Engineering.
The IMRF is pleased to announce that it has funded a project to develop a mouse model for neonatal Marfan syndrome under the direction of Dr. Dirk Hubmacher. Neonatal Marfan syndrome is the most severe form of Marfan syndrome, a connective tissue disorder that affects 1-2 in 5,000 newborns. Most individuals diagnosed with neonatal Marfan syndrome die within their first two years of life due to heart failure caused by an abnormally extended aorta, which is the largest blood vessel in the body, and abnormal heart valves. Dr. Hubmacher’s team will delete a small part of the fibrillin-1 gene in mice to mimic the genetic alteration in the fibrillin-1 gene that was identified in two individuals diagnosed with neonatal Marfan syndrome. The fibrillin-1 gene encodes a protein that is secreted by many cell types and is deposited in connective tissues of blood vessels, the lung, bones, skeletal muscle, and the eye. Once outside of the cell, the fibrillin-1 protein forms cable-like structures that can serve as a scaffold for other components of connective tissues and that can regulate cell behavior and mechanical tissue properties. Ultimately, the goal of the project is to understand why some mutations in the fibrillin-1 gene cause neonatal Marfan syndrome and what makes them different from fibrillin-1 mutations that cause classical MFS. This information can then be harnessed to delineate and test possible treatment strategies for neonatal Marfan syndrome.
IMRF + Icahn School of Medicine at Mount Sinai: Dr. Dirk Hubmacher
IMRF + New York University
The IMRF is pleased to announce it has funded a preclinical study on a cartilage repair formulation under the direction of Dr. Mary Cowman of NYU Tandon School of Engineering and Dr. Thorsten Kirsch of NYU Grossman School of Medicine. Approximately 900,000 Americans experience cartilage injuries to the knee annually, resulting in more than 200,000 surgeries. These procedures lead to the formation of poorly functioning cartilage, and over time, the early onset of post-traumatic osteoarthritis. Drs. Cowman and Kirsch's cartilage repair formulation has the potential to lower the incidence of joint damage due to osteoarthritis and poor repair of soft tissue injuries. They anticipate patients will experience short-term benefits of reduced pain and improved joint functionality after repair, and long-term benefits of reduced risk of post-traumatic, osteoarthritis development.
IMRF + The State University of New York Upstate Medical University
The IMRF is pleased to announce it has funded a Rheumatoid Arthritis-related research proposal under the direction of Dr. Christian Geier. Rheumatoid Arthritis is a painful, inflammatory disease that leads to connective tissue injury; mostly women are affected. Even with modern therapies many patients do not achieve remission, or only do so after irreversible injury to cartilage, bone, tendon and ligaments has already occurred. The proposal seeks to enable better therapies by studying a potentially antigen-presenting cell in RA (which we designate candidate APC) and its function which we anticipate may be pathogenic. By doing so we hope to enable the development of new therapies which target the activation of self-reactive immune cells but leave other aspects of the immune system intact, which could result in more individualized and more effective treatment options for patients living with this potentially debilitating connective tissue disease. Dr. Geier also received the Ines Mandl Connective Tissue Research Fellowship while he was a fellow at Columbia University. (Note: The Ines Mandl Connective Tissue Research Fellowship and the Ines Mandl Research Foundation are not directly related; however, both were founded by Dr. Ines Mandl.)
The IMRF is excited to announce it has funded a research proposal studying issues related to preterm birth under the direction of Dr. Sandra Resnik at St. John’s University. Preterm birth affects 15 million babies a year and is the leading cause of mortality and illnesses with lifelong consequences among neonates. The cervix is an organ composed mostly of connective tissue that serves as the gatekeeper for birth. When this protective barrier transforms into a passage to allow the baby to be born, it undergoes profound structural changes known as cervix ripening. While factors that contribute to causes of preterm birth are varied, ripening results from degradation of collagen structure, a consequence of immune cell mediated inflammation. We have discovered that N,N-dimethylacetamide (DMA), a compound currently used as an “inert” ingredient in many drug formulations, has anti-inflammatory properties that include the prevention of preterm birth in a well-established model of inflammation-induced preterm birth. This proposal partners with an expert in the reproductive immunology of prepartum cervix ripening to determine whether the anti-inflammatory actions of DMA prevent preterm birth by forestalling cervix ripening. Studies in Aim 1 will for the first time compare the time course for ripening in mice rescued from preterm birth by treatments with DMA. In Aim 2, studies will investigate the biomolecular mechanism of action whereby DMA blocks cervix ripening and thereby prevents preterm birth. The principal objective of this project is to identify approaches that will lead to the first approved treatment to prevent preterm birth in women. The ultimate goal is to learn when and how a safe and effective therapy can be provided to prolong pregnancy and ensure the well-being of the newborn in women at risk for preterm birth.
IMRF + St. John’s University
The IMRF has recently funded a research proposal studying adipose tissue under the direction of Dr. Stanton L. Gerson, Director of the Case Comprehensive Cancer Center and the National Center for Regenerative Medicine at Case Western Reserve University. Adipose tissue is specialized connective tissue that functions as the major storage site for fat in the form of triglycerides. Our hypothesis is that adipose is a key regulator of inflammation and regeneration of connective tissues. Adipose is located throughout connective tissues and both impacts and mitigates all diseases of connective tissue. Maintenance of adipose (fat) cells throughout connective tissues likely mitigates inflammation, provides an energy source for connective tissue repair, and provides proper density and interactions between cell types and buffers tissue layers. Adipocytes are the major cell type residing in the adipose tissue, and they are supported and renewed through signals provided by the extracellular matrix (ECM) throughout connective tissue spaces. Dr. Gerson and his team will be studying the means by which the ECM signals the body to produce mature adipocytes. Previous studies suggest that integrin beta-1 (Itgb 1) plays a role in this process. Work by Dr. Gerson and his team are establishing a link between Itgb 1 and peroxisome proliferator-activated receptor gamma (PPARγ). This transcription factor is involved in inflammation of connective tissues, glucose regulation, and diabetes. The specific nature of the interaction between Itgb 1 and PPARγ will be investigated in the study. Understanding these signaling pathways will uncover new approaches to accelerating regeneration and controlling inflammation of connective tissues.
IMRF + Case Western Reserve University
IMRF + The Hebrew University in Jersusalem: Dr. Chaya Kalcheim
The IMRF is pleased to announce its support for Dr. Chaya Kalchaim’s research at the Hebrew University in Jerusalem. Dr. Kalcheim’s research is focused on the embryonic mesoderm. The embryonic mesoderm is the source of most of the body’s connective tissue comprising vertebral cartilage and bone, tendons, dermis, fibroblasts within striated muscles, vascular smooth muscle, etc. In the present project we aim at elucidating the role/s of the morphogen Sonic hedgehog (Shh) in both early and later development of the mesoderm into its derivatives, the molecular targets of Shh activity, and their biological functions.
IMRF + The Hebrew University in Jerusalem: Dr. Joseph Orly
The IMRF is pleased to announce its funding Dr. Joseph Orly’s research at the Hebrew University in Jerusalem. Dr. Orly’s research focuses on cardiac fibroblasts after myocardial infarction. The IMRF grant supports Dr. Orly’s efforts to understand new findings important for the recovery process of the heart after a ‘heart attack’, also named in the medical jargon - acute myocardial infarction (MI). What causes MI is blood clot occlusion of blood vessel(s) feeding the heart muscle, which results in necrotic death of millions of cardiac muscle cells (cardiomyocytes). The loss of the cardiomyocytes is irreplaceable and, therefore, the life of MI patients depends on prevention of heart-wall rupture by the combined activity of the immune system followed by activation of specialized cardiac fibroblasts. The latter resident cells rapidly replace the dead tissue by intensive secretion of elastic collagen “glue” that forms a “scar.” We discovered that while activated by the ischemic catastrophe, the heart fibroblasts also express an unexpected protein named StAR. With support of the IMRF, we show that StAR, normally known to play a vital endocrine role in the adrenal, ovary and testis, has an alternative activity in the heart by protecting the fibroblasts against deadly stress that associates with the inflammatory “cleaning” activity required prior to collagen synthesis. We also show that StAR expression is triggered by interleukin-1a (IL-1a) known to ignite the inflammatory response mentioned above. Our next experiments aim to prove the physiological importance of StAR by using genetically manipulated mice, such as mice lacking IL-1a expression, or mice with no ability to make StAR in the cardiac fibroblasts. We expect that in both models the absence of StAR will result in substantial loss of fibroblasts, which is expected to affect the heart recovery and function after MI. The new understandings might turn beneficial to prevent adverse remodeling of the injured heart and, therefore, reduce the mortality rates after MI.
IMRF + Columbia University: Dr. Hasan Erbil Abaci
The skin is an organ that houses a great number of blood vessels, making it an indispensable route for the delivery of drugs. In light of the growing body of evidence on the diversity of blood vessel presence in different organs, identification of the specifics of the skin’s vascular system would have an overwhelming impact on the delivery of drugs, as well as prevention of drug side effects that commonly manifest on the skin. In an earlier study, Dr. Abaci grafted vascularized 3D human skin constructs (HSCs) onto mice, and showed that blood vessels engineered from human stem cells exhibit similarities to the vasculature present in skin. The hypothesis of this study is that the skin microenvironment induces a distinct molecular and functional microvasculature. In the study, Dr. Abaci and his team will employ their unique vascularized HSC model that replicates the cellular and extracellular microenvironment of the skin to examine the generation and remodeling of the vascular basement membrane (BM).The two main aims of this study are to: 1) examine the remodeling of the dermal extracellular matrix (ECM) by endothelial cells; and 2) dissect the epidermal and dermal cues affecting the skin-specific microvasculature.
IMRF + Columbia University: Dr. Joy-Sarah Vink
It is currently understood that babies born prematurely are at significant risk of death, disability, and lifelong illness. The problem of preterm birth remains a challenging dilemma as the CDC reports about 1 in 10 babies are still born preterm in the US every year. Although extensive research has been done in the field of preterm birth, the rate of spontaneous preterm birth has not significantly decreased in part because we still do not fully understand the mechanisms behind how normally labor begins. As such, we know even less about how the reproductive organs (uterus, cervix, etc.) malfunction in a preterm birth. Dr. Vink’s lab focuses on investigating how the tissue structure of these organs influences their function in pregnancy. Her current work focuses on understanding how the cervix (the structure at the bottom of the uterus that keeps the uterus closed in pregnancy) remodels and softens in pregnancy to allow for delivery of the fetus and how this process is activated prematurely leading to premature cervical dilation/failure and preterm birth. In an earlier study, Dr. Vink discovered that the cervix, which was thought to be a mostly homogenous collagenous structure, contains a significant amount of smooth muscle, which may form a sphincter that keeps the uterus closed until parturition begins. She also found that the type and rigidity of the surrounding cervical tissue extracellular matrix influences the contractility of cervical smooth muscle. Specifically, the smooth muscle does not contract as well when the smooth muscle cells are embedded in soft extracellular matrix. Dr. Vink has also shown that women who have premature cervical failure leading to preterm birth have softer cervical tissue profiles as determined by collagen crosslinking studies. Given that the cervix normally remodels and softens in pregnancy to allow for delivery at term, and women with premature cervical failure leading to preterm birth have “softer” tissue, Dr. Vink’s hypothesis is that the competence of the smooth muscle in the cervical sphincter depends on the type and stiffness of the surrounding extracellular matrix in the cervix. Further, she hypothesizes that in women who deliver preterm, the extracellular matrix proteins are altered – resulting in softer connective tissue that leads to sphincter failure. As such, preterm birth may stem from pathophysiologic alterations in connective tissue proteins and may be considered a connective tissue disease. To test her hypotheses, Dr. Vink’s proposed study will 1) define how the protein profiles change in the cervical extracellular matrix as cervical connective tissue softens in normal pregnancy; and 2) define if the extracellular matrix protein profiles and mechanical properties are altered in cervical connective tissue from women with premature cervical remodeling resulting in preterm birth. These studies are vital to further understanding how the cervix functions and in further developing novel therapies that may one day finally decrease the rate of preterm birth.
The IMRF has recently supported Dr. Sophia Liu’s research on idiopathic pulmonary fibrosis at Mount Sinai Hospital in New York.
Idiopathic pulmonary fibrosis (IPF) is a rare and fatal disease which causes progressive scarring in the lungs making breathing difficult. It prevents the lungs from delivering enough oxygen to the bloodstream for usual activity. The National Institute of Health estimates that approximately 100,000 adults in the U.S. have IPF, as well as approximately 3 to 5 million worldwide. Most affected patients survive 3 to 5 years after diagnosis. There is currently no cure for IPF – the current treatment options are limited to delaying disease progression. At present two FDA-approved IPF drugs - Boehringer’s Ofev and Genetech’s Esbriet work on slowing the inexorable decline in lung function but have variable results. Supplemental oxygen and pulmonary rehabilitation help to relieve the symptoms. Some patients may receive a lung transplant, but others are too frail for the procedure. In idiopathic pulmonary fibrosis, fibroblasts are the main effector cells. Once fibroblasts enter the site of injury, they differentiate into contractile and secretory myofibroblasts, which are the principle source for the scarring tissue. The pharmaceutical companies aim to develop anti-fibrotic therapeutic agents that target disrupting and reducing myofibroblast formation. Two main cytokines, transformation growth factor (TGF-β) and Rho-associated coiled-coil forming protein kinases (ROCK) play critical roles in stimulating the fibroblast/myofibroblast differentiation process. Transformation growth factor β is the most potent and well known cytokine inducer involved in IPF. Though TGF-β inhibitors have been in development for decades with newer agents i.e., RNAi which display manageable toxicities. However, the fact that TGF-β inhibition may result in anti-proliferative effects at low concentrations and pro-proliferative effects at higher concentrations, they might not serve as effective inhibitors for IPF. Therefore, it is worth studying whether ROCK inhibitors have anti-fibrotic effects and if so, the possible mechanisms behind it. In this regard, preclinical research studies in animals have showed that integrin plays a role in TGF-β activation, and integrin αvβ6 knockout mice are resistant to develop pulmonary fibrosis. However, clinical data have shown less promising results, Biogen terminated a phase 2 trial of STX-100, the integrin αvβ6 monoclonal antibody in IPF last month due to safety concerns. Moreover, integrin alpha V beta 6 are expressed exclusively on epithelial cells; however, the main effector cells involved in IPF are fibroblasts, which express integrin alpha v beta 1 mainly on the cell membrane. Previous studies have shown a point mutation in the β1 subunit which abrogates binding of integrin α5β1 to fibronectin without disrupting assembly structure. Therefore it would be informative to evaluate whether a point mutation in β1 subunit in integrin αvβ1 can reduce its binding to TGF-β without disrupting its function and expression. It would also provide a tool to study whether ROCK inducing fibroblast/myofibroblast differentiation is TGF-β dependent or not. Recognizing the above, my plan is to use CRISPR technology, which allows gene specific deletion on the binding site in the β1 subunit of αvβ1 integrin to prevent its binding with TGF-β without disruption of β1 subunit expression, to provide more insight to myofibroblast formation.
IMRF + Mount Sinai Hospital: Dr. Sophia Liu
The IMRF has recently supported Dr. Robert Mecham’s research at the Washington University in St. Louis. Research in the Mecham lab focuses on understanding the biology of microfibrils. These unique matrix structures are found in all tissues from early development through adulthood. Microfibrils band together into large fibers where they have a mechanical role, participate in protein assembly, and regulate growth factor signaling. Their abundance and ubiquity in the ECM of both developing and mature tissues point to an essential role in defining an extracellular environment that influences cellular phenotypes. It is now clear that this “microfibrillar niche” is a significant regulator of tissue development and repair. The vital contributions of the microfibril-associated proteins are just beginning to emerge. Still, it is clear from the broad spectrum of diseases associated with mutation of these proteins that deciphering their functional role is required for understanding the microfibril niche and the molecular basis of human connective tissue disease pathogenesis. The Mecham lab is using advanced light and electron microscopic imaging techniques together with unique animal models to explore microfibril structure and function. Their goal is to understand how microfibrils assemble into functional units and how mutations in microfibrillar proteins lead to disease.
IMRF + Washington University in St. Louis
The IMRF is pleased to announce its funding of Dr. James Segars’ research at Johns Hopkins University in Baltimore. Dr. Segars’ research is focused on uterine leiomyomas.
Uterine leiomyomas are benign uterine tumors that occur in 70-80% of US women. The tumors are composed of cells admixed with an abundant fibrous collagen matrix, with the latter feature invoking the common name of “fibroids.” Treatment options for fibroids are limited and many options have deleterious side effects or unwanted consequences. Given the high prevalence of fibroids and the lack of effective non-surgical therapies, it is important that new treatments are developed. Of note, evidence indicates that collagen deposition plays a key role in fibroid growth and development. Collectively, these findings suggest the hypothesis that collagen degradation by the enzyme, collagenase, may represent a promising therapeutic option for fibroid treatment. We are testing this hypothesis by assessing changes in fibroids treated with collagenase compared to untreated controls. In this research study we will measure the stiffness of the injected fibroids, compared to controls, to assess whether collagenase treatment will soften (melt) the fibroids. In additional experiments we will use histochemical stains and electron microscopy to determine whether collagenase treatment leads to changes in the fibrous tissue (matrix) surrounding the cells within the treated area. In the last set of experiments we will measure several markers of cell growth in the collagenase-treated areas to determine whether cells grow, or stop growing, in the treated areas. This research is the necessary first step toward determining whether collagenase may be a helpful treatment for uterine fibroids. If successful, this treatment might ultimately be offered to women with fibroids who do not want a hysterectomy.
IMRF + Johns Hopkins University
The IMRF has recently supported Dr. Mathias Bostrom's research on total knee replacement at the Hospital for Special Surgery in New York. Specifically, Dr. Bostrom is studying how bone mass affects osseointegration. The grant represents an exciting milestone for the IMRF, as it is the Foundation's first international project. The grant, in conjunction with a stipend from the American Austrian Foundation, will allow an Austrian researcher from Vienna to work in Dr. Bostrom's New York lab.
IMRF + The Hospital for Special Surgery
The IMRF has teamed up with Drs. Mary K. Cowman and Jin Ryoun Kim of NYU’s Tandon School of Engineering to support their research of serum amyloid A. Serum amyloid A is a protein that has been implicated in connective tissue diseases such as rheumatoid arthritis and psoriatic arthritis. The partnership is especially meaningful to the IMRF as Dr. Mandl was the first female graduate of the Polytechnic Institute of Brooklyn, which merged with NYU in the 2000s.
IMRF + New York University Tandon School of Engineering
The IMRF is pleased to have supported the Campion Fund's workshop, **Uterine Fibroids: A Case for Women’s Health** held in Durham, North Carolina, on March 11, 2017. The workshop was a resounding success by all accounts, featuring a number of presentations by doctors from Johns Hopkins to Duke to North Caroline Central University.
According to the Campion Fund, "The purpose of the meeting was to raise awareness among women of our region regarding uterine fibroids and to the need for increased treatment options. Although, classified as non-malignant tumors, uterine fibroids affect 80% of black women and 70% of white women and are a serious public health problem. The develop around the time of menarche and appear to regress at menopause and grow at different rates. The can develop to various sizes, sometime to a tumor of 20 centimeters, or the size of a five-month pregnancy. They cause pain and serious uterine bleeding and can thus cause severe anemia. In addition, uterine fibroids may interfere with the ability to conceive and they are responsible for pregnancy complications including preterm birth. This debilitating disease has not had the attention it deserves from either the medical or scientific communities. Studies estimate that the costs of this disease to the US pubic and health care system is up to $34.4 billion yearly."
A video of the conference will be posted to this website shortly. For more information, please visit the Campion Fund's website: www.campionfund.org