Musculoskeletal Undergraduate Research Internship Program

The BWH Musculoskeletal (MSK) Research Center Internship Program is seeking motivated students interested in pursuing biomedical research within the specific areas of bones, joints, muscles and the disorders that affect them.

Internship programs at the BRI will provide undergraduate students with a focused and challenging summer research training experience in a cutting-edge science laboratory based out of Brigham and Women’s Hospital.

 

MSK INVESTIGATOR RESEARCH SUMMARIES

Anuj Bellare, PhD

Lead Investigator, Orthopedic Nanotechnology Laboratory
Brigham & Women’s Hospital
Assistant Professor, Harvard Medical School
Lab website

The Orthopedic Nanotechnology Laboratory conducts research on orthopedic biomaterials used in implant applications, such as total joint replacement prostheses and spinal implants. In this summer project, the trainee will learn how to chemically modify polymeric biomaterials, such as polyaryl ether ketones, polylactide and polycaprolactone by grafting pendant groups like phosphates, acids or alcohols on to the backbone of the host polymer to increase interfacial strength between the host polymer and nanoparticles of hydroxyapatite. The chemical changes will be characterized by Fourier Transform Infrared Spectroscopy and Energy dispersive X-rays using a scanning electron microscope at the Center for Materials Science and Engineering at MIT. At the end of the training the trainee will have learned how to chemically modify polymers and to characterize and quantify the graft content with the long term goals of tailoring bone tissue-implant interactions to increase the fixation strength of implants. The trainee will also be taught how to write a one-page scientific conference paper, which will be submitted to the Annual Meeting of the Orthopedic Research Society or for the Annual Meeting of the Society for Biomaterials. The skills learned from this project will help the trainee in being able to pursue higher education or a career in the area of biomaterials, especially load bearing orthopedic biomaterials.

Jeffrey Duryea, PhD

Associate Professor, Harvard Medical School
Department of Radiology, Brigham and Women’s Hospital
Lab website

My group, The Quantitative Musculoskeletal Imaging Group (Q-MIG) in the Radiology Department at Brigham and Women’s Hospital specializes in developing software image analysis methods to quantify structural changes related to musculoskeletal diseases. The primary focus is on osteoarthritis (OA) but we have substantial experience with rheumatoid arthritis (RA) and with various animal models to investigate more general disease processes. The overall goal of the program is to provide clinical researchers with fast and objective methods that can facilitate high-powered studies and clinical trials.

For a potential intern, familiarity and general competence with the Windows operating system is important.  Since the research involves MRI and radiographic imaging of arthritic joints, this is an ideal position for students with an interest in Radiology, Orthopedics, or Rheumatology and a career in academic medicine.  There is an opportunity for co-authorship on publications depending on the performance of the individual.

Julie Glowacki, PhD

Glowacki Lab:
Julie Glowacki, PhD

Director, Skeletal Biology Research Laboratory
Professor of Orthopedic Surgery, Harvard Medical School
Professor of Oral & Maxillofacial Surgery, Harvard School of Dental Medicine

Dr. Glowacki studies mechanisms of skeletal pathology, aging, and impaired fracture and wound healing.  Common skeletal disorders include osteoarthritis, osteoporosis, and impairments in healing of traumatic injuries.  Risk factors for skeletal disease are being investigated.  This program includes stem cell and drug discovery approaches to identify novel approaches to those common orthopedic problems.  Students have the opportunity to receive training in methods of cell culture, gene expression analyses, histology, statistics, and scientific writing.

Shuichi Mizuno, PhD

Assistant Professor of Orthopedic Surgery

Brigham & Women’s Hospital

Our research program covers the mechanobiology of articular cartilage and intervertebral discs, as well as tissue engineering applications in biological repair for articular cartilage defects and meniscal tears.

Mechanobiology in Articular Cartilage and in Intervertebral Disc

We have focused on the mechanobiology in three-dimensional cartilage histogenesis and in intervertebral disc homeostasis in response to changes in physicochemical stresses. Articular cartilage has distinct tissue morphology in longitudinal depth.  In addition, the intervertebral disc has amorphous nature.  Moreover, both tissues have to withstand on weight-bearing and joint-loading.  Thus, we have studied mechanisms of degeneration, regeneration, and homeostasis due to the stresses using our novel cell culture system that allows changes in hydrostatic pressure, oxygen concentration, distortional stress (shear or deviatoric stress), and osmotic pressure.  New information will help to develop cell-based therapies and drug discovery in musculoskeletal tissues.

Biological Repair for Articular Cartilage Defects and Meniscal Tear to Prevent Early Osteoarthritis

We have been developing a novel injectable cell/matrix for promoting meniscal repair and articular cartilage regeneration using a semipermeable membrane pouch, amorphous cell carrier, and our novel cell culture system.  Because meniscal tear and cartilage defects are often found at the same time in adolescents, biological treatments for these wounds will be useful and valuable for reducing post-traumatic osteoarthritis.  Desired cells treated with physicochemical changes will promote wound healing in meniscal tear and cartilage defects.

Nancy Shadick, MD, MPH

Shadick Lab

Dr Shadick is considered a leader in the field of Lyme Disease. In a landmark and widely quoted study in the Annals of Internal Medicine, she was the first investigator to validate using population-based analyses the phenomenon of incomplete recovery. In individuals with previously treated illness, there was a higher prevalence of neurocognitive deficits and musculoskeletal sequelae compared with those without LD especially in those with a longer duration of infection. This paper lead to a recognition that the current antibiotic therapy was inadequate and lead to a change in treatment recommendations. This paper also broke ground in that it identified, prior to SPECT scanning and other functional neuroimaging, that Lyme encephalopathy was a disorder of attention and concentration and therefore a white matter disease. Years later, this observation was confirmed on functional MRI scans. This paper led to an NIH Arthritis Center grant to establish the “Nantucket Island Lyme Disease Cohort”. In the Annals of Internal Medicine this follow up study demonstrated that the long term outcomes of LD were improved with intravenous cephalosporin therapy and earlier diagnosis. It noted that those with initial symptoms of neurological dissemination tended to have poorer outcomes and led to acceptance of more aggressive antibiotic therapy. A third paper, in the Annals of Internal Medicine addressed whether there were late cardiac sequelae after LD and documented favorable outcomes (8) and another noted that children infected with LD recovery quite completely. Dr Shadick’s work on the long term outcomes of LD is widely referenced and quoted as authoritative in the area of LD clinical management.

  1. Shadick NA, Phillips CB, Logigian EL, Steere AC, Kaplan RF, Berardi VP, Duray PH, Larson MG, Wright EA, Ginsburg KS, Katz JN, Liang MH. The long-term clinical outcomes of Lyme disease. A population-based retrospective cohort study. Ann Intern Med 1994;121:560-7
  2. Shadick NA, Phillips CB, Sangha O, Logigian EL, Kaplan RF, Wright EA, Fossel AH, Fossel K, Berardi V, Lew RA, Liang MH. Musculoskeletal and neurologic outcomes in patients with previously treated Lyme disease. Ann Intern Med 1999;131:919-26.
  3. Sangha O, Phillips CB, Fleischmann KE, Wang TJ, Fossel AH, Lew R, Liang MH, Shadick NA. Lack of cardiac manifestations among patients with previously treated Lyme disease. Ann Intern Med 1998;128:346-53
  4. Wang TJ, Sangha O, Phillips CB, Wright EA, Lew RA, Fossel AH, Fossel K, Shadick NA, Liang MH, Sundel RP. Outcomes of children treated for Lyme dis¬ease. J Rheumatol 1998;25:2249-53.

 

Dr Shadick’s LD prevention research has also significantly impacted the field. With Dr. Matthew Liang, she developed the first educational program to effectively reduce the incidence of LD (7,21).  Data from this study led to the current UO1 grant to develop an educational program of LD prevention for children. Dr Shadick created a curriculum in collaboration with the Mass. Dept. of Public Health and the CDC which is now integrated into the North Shore school system of Mass. and nationwide.

  1. Shadick NA, Daltroy LH, Phillips CB, Liang US, Liang MH. Determinants of tick-avoidance behaviors in an endemic area for Lyme disease. Am J Prev Med 1997;13:265-70.
  2. Phillips CB, Liang MH, Sangha O, Wright EA, Fossel AH, Lew RA, Fossel KK, Shadick NA. Lyme disease and preventive behaviors in residents of Nantucket Island, Massachusetts. Am J Prev Med 2001;20:219-24.
  3. Daltroy LH, Phillips C, Lew R, Wright E, Shadick NA, Liang MH. A controlled trial of a novel primary prevention program for Lyme disease and other tick-borne illnesses. Health Educ Behav 2007;34:531-42
  4. Shadick NA, Maher NE. Tick Borne Diseases in Massachusetts: a Physician’s Desk Reference Manual. 2002.

 

Dr Shadick’s current research focuses on defining outcomes in RA. As a rheumatology fellow, she described a novel comorbidity in RA: bronchiectasis.  Published in Medicine she described this illness as an ominous comorbidity in patients with severe and longstanding disease that dramatically reduced a patient’s lifespan. After the report, bronchiectasis became recognized as a new RA comorbidity that is currently screened for and treated much earlier. In 2003, Dr Shadick founded one of the largest single center cohorts of RA in the nation; the Brigham & Women’s Hospital RA Registry (BRASS). This Registry of over 1400 subjects followed yearly has contributed to a number of manuscripts of which Dr Shadick has been an integral investigator. Dr. Shadick’s current primary contributions in the field of RA include delineating clinical and genetic phenotypes that traditionally have defined RA disease susceptibility as markers of disease severity. Dr. Shadick’s data demonstrated that the genetic marker the D70 allele of the HLA region had a significant protective effect on disease severity independent of the shared epitope. Both of these papers are widely quoted in the RA literature as illuminating that genetic risk factors for disease onset can also predict severity and clinical phenotype.

  1. Shadick NA, Fanta CH, Weinblatt ME, O’Donnell W, Coblyn JS. Bronchiesctasis: A late feature of severe rheumatoid arthritis. Medicine 1994;73:161-70.
  2. Cui J, Taylor KE, Destefano AL, Criswell LA, Izmailova ES, Parker A, Roubenoff R, Plenge RM, Weinblatt ME, Shadick NA*, Karlson EW*. Genome-wide association study of determinants of anti-cyclic citrullinated peptide antibody titer in adults with rheumatoid arthritis.  Mol Med 2009;15:136-43.  PMCID: PMC2654848
  3. Iannaccone C, Lee Y, Cui J, Frits M, Glass R, Plenge R, Solomon D, Weinblatt M, Shadick N. Using genetic and clinical data to understand response to disease-modifying anti-rheumatic drug therapy: data from the Brigham and Women’s Hospital Rheumatoid Arthritis Sequential Study. Rheumatology (Oxford) 2011;50(1):40-6.  doi: 10.1093/rheumatology/keq263. Epub 2010 Sep 16.
  4. Shadick NA, Sowell NF, Frits ML, Hoffman SM, Hartz SA, Booth FD, Sweezy M, Rogers PR, Dubin RL, Atkinson JC, Friedman AL, Augusto F, Iannaccone CK, Fossel AH, Quinn G, Cui J, Losina E, Schwartz RC. A Randomized Controlled Trial of an Internal Family Systems-based Psychotherapeutic Intervention on Outcomes in Rheumatoid Arthritis: A Proof-of-Concept Study.  J Rheumatol 2013;40(11):1831-41. doi: 10.3899/jrheum.121465. Epub 2013 Aug 15.

 

In a seminal study of risk factors for RA onset in collaboration with the Women’s Health Study, Dr. Shadick investigated the role of C-reactive protein in women in the Archives of Internal Medicine.  Prior studies had demonstrated that years before RA diagnosis, autoantibodies such as anti-CCP and RF are present in the blood.   The study noted that unlike the other autoantibodies, CRP level did not predict increased risk of RA. In a companion paper with Dr Elizabeth Karlson from the same cohort, Vitamin E was similarly found not to be protective of RA onset. Previous conventional wisdom suggested that anti oxidant intake may be protective against autoimmune disease and this study proved otherwise. However, in a subsequent paper in the WHS and Nurse’s Health Study, Dr Shadick found that TNF receptor II and IL-6 were found to be elevated years prior to disease onset which illuminated the pre-clinical immunological abnormalities in RA and expanded opportunities to study RA prevention.

  1. Shadick NA, Cook NR, Karlson EW, Ridker PM, Maher NE, Manson JE, Buring JE, Lee IM. C-reactive protein in the prediction of rheumatoid arthritis in women. Arch Intern Med 2006;166:2490-4.
  2. Karlson EW, Shadick NA, Cook NR, Buring JE, Lee IM. Vitamin E in the primary prevention of rheumatoid arthritis: The women’s health study. Arthritis Rheum 2008;59:1589-95. PMCID: PMC2927963
  3. Karlson EW, Chibnik LB, Tworoger SS, Lee IM, Buring JE, Shadick NA, Manson JE, Costenbader KH. Biomarkers of inflammation and development of rheumatoid arthritis in women from two prospective cohort studies. Arthritis Rheum 2009;60:641-52. PMCID: PMC2715148
  4. Shadick NA, Karlson EW, Cook NR, Maher NE, Buring JE, Lee IM. Low-dose aspirin in the primary prevention of rheumatoid arthritis: The Women’s Health Study. Arthritis Care Res 2010;62(4):545-50.  PMCID:PMC2990344

Jessica Whited, PhD

Whited Lab

Axolotl salamanders are vertebrates whose limbs closely resemble human limbs in form and function, yet they can be completely regenerated throughout life following amputation.  My laboratory aims to understand this process at a detailed molecular, genetic, and cellular level with the hope that this increased scientific understanding will provide crucial clues to the more limited regenerative abilities of mammals such as humans.  Two essential features of axolotl limb regeneration are the formation of a specialized wound epidermis and the creation of a pool of progenitor cells, collectively called the blastema.  Using discovery-based methods, we have identified genes functioning in these two populations to promote successful regeneration.  We are currently interrogating the mechanisms of their activities using modern tools such as transgenesis, gene editing, and retroviral infections in vivo.  In the long-term, the laboratory is interested in extending these studies into mammals and, ultimately, humans in collaboration with other researchers and clinicians at BWH/HMS.

Shuanhu (Joe) Zhou, PhD

Zhou Lab
Shuanhu (Joe) Zhou, PhD

Associate Scientist, Brigham and Women’s Hospital
Assistant Professor of Orthopedic Surgery, Harvard Medical School

Bone is a living tissue that deteriorates with aging due to an imbalance between the activity of cells that continuously generate new bone and cells that resorb old bone. Cells that produce new bone, osteoblasts, differentiate from a type of adult stem cells — mesenchymal stem cells (MSCs), which are also the progenitors of chondroblasts that form cartilage, and adipocytes that develop into fat.  Our recent studies concern MSCs from mice and human.  Current research projects investigate (1) the effects of aging on human MSCs; (2) how the aging cellular microenvironment (niche) of these stem cells may contribute to their declining ability to generate new bone-producing cells; (3) the roles of vitamin D in pathophysiology of skeletal systems; (4) the roles of aging mechanisms in the development of osteoarthritis and cartilage tissue engineering. The overall goal of our research is to contribute new information to basic skeletal biology and orthopedic science using human primary cells, and to understand the mechanisms of skeletal aging and to develop new therapeutic approaches for aging-related skeletal diseases.

Katherine P. Liao, MD, MPH

Associate Physician, Brigham and Women’s Hospital
Assistant Professor of Medicine, Harvard Medical School

 

Dr. Liao is a clinical investigator and practicing rheumatologist. The mission of her lab her lab is two-fold: (1) is to study rheumatoid arthritis (RA), and the clinical and genetic factors that lead to outcomes such as cardiovascular disease and severe joint damage, and (2) is to apply and develop bioinformatics methods to utilize big data for clinical and translational research studies. Dr. Liao’s research focuses on applying methods such as natural language processing to electronic medical record (EMR) data to perform clinical studies in RA and other conditions.

Heart disease is the leading cause of death in patients with RA. This high risk has been attributed to inflammation, which is an important risk factor for heart disease in the general population. Determining these links can identify strategies to reduce CV risk in RA, as well as lead to potential targets of treatment in the general population. Dr. Liao is the PI of the R01 funded study, Lipids, Inflammation and CV risk in RA (LiiRA). The goal of LiiRA is to investigate how inflammation may modify important traditional cardiovascular risk factors such as cholesterol and blood pressure, and the impact of these modifications on CV risk. She is also a co-investigator on an NIH U01 multi-center RCT, Treatment Against RA and Effect on FDG PET CT (TARGET). TARGET specifically tests the hypothesis that reducing inflammation, reduces vascular inflammation and CV risk in RA. In line with her research interests, Dr. Liao is co-Director of the Cardiovascular Rheumatology Clinic at Brigham and Women’s Hospital.

Through her work with the Informatics for Integrating Biology and the Bedside (i2b2) project, Dr. Liao led the team to develop an EMR research platform for RA studies. This platform integrated clinical and biomarker data (e.g. clinical EMR data, genetics, autoantibody data) allowing for both traditional genetic association studies as well as new approaches for data analyses such as the Phenome Wide Association Study (PheWAS). Using this platform, she collaborates closely with investigators from the fields of biostatistics and bioinformatics to apply novel methods to study focused clinical questions such as CVD in RA. Currently, she is leading a pilot project to port and further develop these methods at VA Boston Healthcare using nationwide VA data with a goal to establish an EMR research platform at the VA.

Karen H. Costenbader, MD, MPH

Rheumatologist, Brigham and Women’s Hospital
Associate Professor of Medicine, Harvard Medical School

 

Dr. Costenbader’s lab conducts epidemiological and outcomes research on rheumatic diseases, in particular Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE).  Our group has developed innovative epidemiologic tools for testing hypotheses in populations, investigated the epidemiology of rheumatic diseases in large cohorts of female health professionals, studied predictors of outcome in RA and SLE and established a large SLE Registry.

 

In recent work, our group has studied associations between cigarette smoking and RA and SLE, postmenopausal hormones and oral contraceptive use and risk of SLE, antioxidants and vitamin D intake and the risks of RA and SLE. We are investigating novel biomarkers and causal pathways in the development of RA. Our group also studies predictors of outcomes, including cardiovascular disease, lymphoma, nephritis and end-stage renal disease, among patients with SLE, and sociodemographic disparities in the incidence and outcomes of SLE in the U.S. The BWH Lupus Registry includes >1700 SLE patients from BWH and the BWH Lupus Biobank, housed at the Broad Institute, contains stored samples on many of this cohort. We are currently investigating biomarkers of SLE activity and disease risk, whether high dose vitamin D and/or fish oil intake are effective in the prevention of autoimmune disease, and access to care and outcomes among patients with SLE.

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