Department of Pathology News

Repairing nerve cell damage from multiple sclerosis

Tuesday, June 17, 2014

Dr. Bridget-Shafit Zagardo investigates how to repair nerve cell damage from multiple sclerosis.

















Each year multiple sclerosis (MS) strikes millions of young adults in the United States and worldwide, limiting their mobility, causing disability and pain, and seriously affecting their quality of life. Onset is observed in young adults in their 20's and 30's, with a pediatric form of MS becoming increasingly prevalent. While various current treatments delay progression or manage the symptoms, there is currently no cure and there is significant decline over a 15-20 year period with a large number of patients progressing from a relapsing remitting disease course to a progressive disease course.

For over 30 years, Einstein Pathology researcher Bridget Shafit-Zagardo, PhD, has worked to understand MS and give people suffering from the neurological disease hope.

“We’re predominantly interested in enhancing repair and functional recovery following central nervous system (CNS) injury,” said Dr. Shafit-Zagardo, a professor of pathology, who joined Einstein in 1984.



Enhancing repair



She explained that MS damages neurons, or nerve cells, and the myelin sheath - the insulation that surrounds and protects axons. The loss of myelin – demyelination - interferes with the transmission of normal nerve conductance required for nerves to signal between the brain, spinal cord and the rest of the body. 

“The goal is to repair axonal damage and enhance remyelination,” she said, noting that the current treatments address inflammation, but do not address nerve cell repair.

The exact antigen — or target that the immune cells are sensitized to attack — remains unknown, which is why MS is considered by many experts to be "immune-mediated," she said.

Abnormally hyper-activated infiltrating immune cells cross the blood brain barrier and induce inflammation in the CNS. As a result, resident cells of the CNS become activated and secrete inflammatory molecules that further enhance inflammation resulting in damage to neurons and oligodendrocytes, the myelin-synthesizing cells of the CNS. Axonal damage, destruction of myelin and activation of astrocytes called astrogliosis, ultimately result in CNS lesions referred to as glial scars or plaques in areas of damage. The resulting insult affects nerve fibers producing symptoms that may affect vision, coordination and mobility, and continence, among other symptoms.  

To that end, Dr. Shafit-Zagardo and her team are investigating strategies to slow the progression of axonal damage and demyelination and to enhance remyelination.

“Until damaged myelin and cell debris resulting from inflammation are cleared, you do not have efficient repair and recovery cannot occur,” said Dr. Shafit-Zagardo. The lab’s ongoing projects include applying techniques of molecular & cell biology, biochemistry, immunocytochemistry, confocal and electron microscopy to address questions concerning the structure, function and regulation of myelination in the normal CNS and remyelination following neuroimmune injury.



Identifying signaling pathways



Central to the treatment of MS is how cell signaling pathways regulate oligodendrocyte cell survival and remyelination after the inflammatory response.
Toward this goal, the lab has used molecular approaches to identify several genes implicated in signaling pathways that regulate oligodendrocytes and protect against demyelination. Among those genes identified were members of the Tyro3/Axl/Mer (TAM) family of receptor tyrosine kinases. As Dr. Shafit-Zagardo explained, to clear debris in MS lesions, the ligand or growth factor binds to receptors on the cell and signals downstream, recruiting signaling molecules that are protective for survival of the cell and also serve to activate other signaling pathways necessary for repair. The lab has demonstrated that signaling through the growth arrest-specific protein 6 (Gas6)/TAM pathway protects oligodendrocytes against injury.

Dr. Shafit-Zagardo’s research is funded by grants from the National Multiple Sclerosis Society and the National Institute of Neurological Disorders and Stroke. Assisting Dr. Shafit-Zagardo in her research is postdoctoral fellow Ross Gruber, graduate student Alex Ray and technician Kathleen O’Guin. Ross and Alex have been generating different mouse models, including single and double knockout mice that can be used to study different signaling pathways.



Moving forward



Despite her many achievements both inside and outside of science, the Bronx native has not had to venture far. After earning her master’s degree in biology at New York University, she studied human genetics with Dr. Robert Desnick and was awarded a PhD from City University of New York/ Mount Sinai School of Medicine, where her research focused on lysosomal storage diseases focusing on Gaucher’s disease. She initially joined Einstein as a postdoctoral research fellow under the mentorship of Dr. Joseph Maio in Cell Biology, working on long interspersed repetitive sequences. Dr. Shafit-Zagardo became involved in MS after seeing that early developmental genes could be turned back on during remyelination, and continued to expand on those initial studies.

MS research has come a long way in the last two decades. “Thirty years ago, there were no real treatments,” Dr. Shafit-Zagardo said, noting that the last 20 years has seen a variety of medications used for MS to block inflammation, but they do not target myelin repair.

Moving forward, her lab will continue to work toward developing better treatment and attempt to attempt to find factors that can aid in repair. She said, “Once we’ve determined how signaling occurs we will be able to use this information to protect against further damage."





Recent News 

Cross-Campus Collaborations 

Recent Grants

joan-bermanJoan W. Berman, PhD, professor of pathology and of microbiology & immunology, and the Irving D. Karpas MD Chair of Excellence in Medical Research at Einstein, has been awarded a $3.5 million R01 grant from the National Institute on Drug Abuse to study the opioid derivate Bupenorphine as a potential therapy for neurocognitive symptoms in HIV patients.

 

Thanks to antiretroviral drugs, fewer HIV-infected people experience frank dementia, but more than half of those treated with anti-retrovirals suffer from milder, lifelong HIV-associated neurocognitive disorders, or HAND. Joan W. Berman, PhD, has been awarded two NIH grants totaling $7.4 million to study the sequence of events that lead to HAND; examine how certain drugs of abuse increase the risk for HAND; and develop strategies for preventing the disorder.  

  

Dr. Berman and Susan Morgello, MD, of Mount Sinai Icahn School of Medicine, were awarded a five-year, $3.6 million grant from the National Institute of Mental Health to study a population of white cells known to be responsible for HAND. The researchers will follow the migration of these cells in HIV-positive patients and study the proteins that regulate the transit of white cells across the blood brain barrier. The research may lead to therapies that block HIV-infected white cells from entering the brain. (1R01MH112391-01A1)

 

  

Dr. Berman and Harris Goldstein, MD, have been awarded a five-year, $3.8 million grant from the National Institute on Drug Abuse to study the interactions among methamphetamines and other drugs of abuse, antiretroviral therapeutics and HIV infection. The researchers hypothesize that methamphetamines and some anti-retrovirals weaken the integrity of the blood brain barrier, making it easier for HIV-infected white blood cells to enter the brain. Their research will also use a mouse model of HIV. Dr. Goldstein is professor of pediatrics and of microbiology & immunology and director of the Einstein-Rockefeller-CUNY Center for AIDS Research. He holds the Charles Michael Chair in Autoimmune Diseases at Einstein. (1R01DA044584-01) 

 

chandan-guhaChandan Guha MBBS, PhD, has been awarded a five-year, $2.3 million NIH grant to develop measures to prevent radiation-induced vascular injury (RIVI). In collaboration with Janssen Pharmaceuticals, Inc., Dr. Guha and colleagues will test whether the drug Thrombopoietin Mimetic can protect against vascular injuries caused by radiation. Dr. Guha is director of the Einstein Institute for Onco-physics, professor and vice chair of radiation oncology, and a professor of pathology and of urology at Einstein and Montefiore. (1U01AI133608-01) 

 

DavidFooksmanDavid Fooksman, PhDhas received a $417,500 R56 grant from the National Heart, Lung and Blood Institute to investigate myeloid-cell regulation of plasma cell engraftment into bone marrow. Dr. Fooksman is an assistant professor of pathology and of microbiology & immunology at Albert Einstein College of Medicine. 

Research

Experimental pathology aims to define disease in terms of fundamental molecular and cellular processes. Research in our Department is focused on critical issues in multiple disease classes. Areas of focus include 

Research in each of these areas is highly interactive, and the Department strives for a collegial atmosphere in which collaborations can flourish. This effort is conducted through a variety of department-level activities, including regular meetings to discuss work in progress and a departmental retreat at which students, postdoctoral fellows, residents and faculty all have opportunity to present and discuss their research.

Research Funding Program

The Department of Pathology has established a research funding program to encourage residents and fellows to participate in clinical pilot research projects. Up to $2,000 will be awarded per research project, for projects of up to two years in duration.

Research Faculty

Amanda Beck, DVM 

Geoffrey Childs, PhD 

Joan W. Berman, PhD 

Mahalia Desruisseaux, MD, PhD 

Amy Fox, MD  

David Fooksman, PhD  

Rachel Hazan, PhD 

Lawrence Herbst, DVM, PhD 

Huan Huang, MD 

Sunhee C. Lee, MD  

Fernando Macian, MD, PhD 

Maja Oktay, MD, PhD 

Harry Ostrer, MD 

Thomas J. Ow, MD 

Michael B. Prystowsky, MD, PhD 

Moshe Sadofsky, MD, PhD 

Laura Santambrogio, MD, PhD 

Bridget Shafit-Zagardo, PhD 

Herbert Tanowitz, MD 

Louis Weiss, MD 

 
 

Awards, Honors & Appointments

Michael PrystowskyMichael B. Prystowsky, MD, PhD, FCAP, Professor and University Chair of Pathology at Montefiore Einstein, has received the College of American Pathologists (CAP) President’s Honor. The award, which recognizes “outstanding and dedicated service to Pathology and to the College of American Pathologists,” was presented by Richard C. Friedberg, MD, PhD, FCAP, outgoing CAP President, at the CAP annual meeting in October. Dr. Friedberg thanked Dr. Prystowsky -- a longtime CAP fellow, a governor of the College, and a past chair and current vice chair of its Council on Education -- for his “thoughtful assessments” and “calm and analytical discussion, counsel and debate.” He added, “Michael’s enthusiasm to educate is legendary, and he has been a tremendous asset to the educational mission of the CAP. Residents around the world have benefitted from his analytical mind.”  Photo: Dr. Michael Prystowsky, right, with Dr. Richard Friedberg, immediate past president, College of American Pathologists, at the 2017 CAP annual meeting. 
 

Mark SuhrlandMark J. Suhrland, MD, director of cytology at Montefore and a professor of pathology at Albert Einstein College of Medicine, has received the College of American Pathologists (CAP) Foundation’s 2017 Herbek Humanitarian Award. The award was presented to Dr. Suhrland by Karim Sirgi, MD, CAP Foundation President, at the 2017 CAP annual meeting held in National Harbor, MD, in October. The Herbek award is bestowed on a CAP Fellow who provides outstanding direct patient services to individuals in underserved communities through a See, Test & Treat program. The award includes a grant which Dr. Suhrland will use to fund the production of public health brochures aimed at educating parents about the importance of HPV vaccinations for pre-teens and teens. The brochures will be distributed to attendees at Montefiore’s See, Test & Treat event in spring 2018. Photo: Dr. Karim Sirgi, CAP Foundation president, left, presents Herbek Humanitarian Award to Dr. Mark Suhrland, at CAP17.  Read more. 

 laura Laura Santambrogio, MD, PhDprofessor of pathology, of microbiology & immunology, and of orthopaedic surgery at Einstein, has had a busy spring, summer and fall. In May, Dr. Santambrogio was an invited speaker at the American Association of Immunologists annual meeting in Washington, DC, where she also served as leader of the Immunology Teaching Interest Group and organized the Block Symposium on Antigen Processing and Presentation. In July, she was an invited speaker at a Symposium on Proteostasis and Aging, in San Francisco. In September, she served as co-organizer of the 9th International Conference on Annexins, held in Cold Spring Harbor, NY. In October, she was an invited speaker at Jefferson University, Philadelphia, PA; Instituto Galeazzi, Milan, Italy; and Instituto Gaslini, Genoa, Italy. 

 

 James_SzymansiRandin NelsonRandin Nelson, MD, and James Szymanski, MD, are recent recipients of the AABB-Fenwal Transfusion Medicine Fellows (TMF) Scholarship Award. Funded by Fresnius Kabi, the TMF Awards Program recognizes professionals with a Doctor of Medicine or Doctor of Osteopathic Medicine degree who are current fellows in a Transfusion Medicine program or training program that includes at least one continuous year in Transfusion Medicine training. Recipients receive a $1,500 honorarium. 

Drs. Nelson and Szymanski are both graduates of the Montefiore Einstein Pathology Residency Program. Dr. Nelson completed his residency in 2014 and went on to do a two-year fellowship in Transfusion Medicine at the National Institutes of Health (NIH) in Bethesda, MD. He recently joined Montefiore Einstein as director of the Stem Cell Processing Laboratory and assistant director of Transfusion Services. Dr. Szymanski completed his residency in 2016. He is presently a fellow in Transfusion Medicine at the NIH. 

 

 MayaMaja H. Oktay, PhD, MD, has been promoted to the rank of Professor of Pathology. Dr. Oktay is a co-author of a study recently published in Science Translational Medicine (To read more, see Recently Published Research). 

 

 

 

 Nicole PanarelliNicole C. Panarelli, MD, has been promoted to the rank of Associate Professor of Pathology.  

 


 

 

 

 LeanaSerannoLeana Serrano-Rahman, MPH, (MT) ASCP, (CQA) ASQ, Blood Bank Manager, Moses, Weiler and Wakefield Divisions, is the lead author of a study, “Blood Management: One Hospital System Experience,” which was selected for display at the annual meeting of the AABB, held in San Diego, CA, in October. The study showed how an interdisciplinary committee successfully collaborated to reduce blood-product expenditures at Montefiore by nearly $1M in 2016 (as compared to 2015) despite higher patient volumes and a more complicated patient mix. Ms. Serrano-Rahman’s co-authors are Mallika Gupta, MBA, MPH, senior business operations consultant, Performance Excellence department; Susan Solometo, former vice president, Clinical Services; Ronald P. Walsh, MD, associate director, Transfusion Services; and Joan M.Uehlinger, MD, director of Transfusion Services at Montefiore and professor of pathology and of medicine (hematology) at Einstein. Ms. Serrano-Rahman represented the group in a poster session at the AABB meeting. The abstract will be printed in Transfusionthe AABB journal.   

RECENTLY PUBLISHED RESEARCH

In recent months, research studies by Pathology Department faculty members and trainees have been published in prestigious, peer-reviewed scientific journals.   View a sampling of these articles here.  

 

TRAINEE SPOTLIGHT

 

Matias Jaureguiberry-BravoMatias Jaureguiberry-Bravo, PhD 5th Year:  

Exploring a Novel Approach to Preventing HIV-Associated Brain Disorders    

  

 

NEW FACES

Welcome! 

New Faculty 

 

   

Debora Nautcsh Deborah Nautsch, MD, , has joined the Department of Pathology, in the Division of Surgical Pathology at Montefiore Medical Center, Montefiore New Rochelle and Montefiore Mount Vernon. Dr. Nautsch comes to us from InCyte Diagnostics in Yakima, WA. She earned her medical degree at Albert Einstein College of Medicine in 2011, and completed a Pathology Fellowship in GI/Liver at Montefiore in 2016.

 

 

  

Jennifer Oliver Jennifer Oliver-Krasinski, MD, has joined Montefiore Einstein as an attending physician in pediatric pathology, division of surgical pathology.

 

 

  

Shwerta Gera Shweta Gera, MD has joined Montefiore Einstein as an attending physician in cytology. Dr. Gera completed a fellowship in cytology at Montefiore Einstein in June 2017.

 

 

  

Randin Nelson Randin Nelson, MD, a 2014 graduate of the Montefiore Einstein Pathology Department’s residency program, has joined Montefiore Einstein as director, Stem Cell Processing Laboratory, and assistant director, Transfusion Services. 

 

New Residents  

RidinRidin Balakrishnan, MD. Dr. Balakrishnan comes to the Montefiore Einstein from Weill Cornell Medical College in Qatar. 

 

 

Angela-BaldwinAngela Baldwin, MD, MPH. Dr. Baldwin earned her medical degree at Howard University College of Medicine and her MPH at University of California San Francisco.

 

 

Mohammad-BarouqaMohammad Barouqa, MD. Dr. Barouqa is a graduate of the University of Jordan Faculty of Medicine in Amman, Jordan.

 

 

George-LominadzeGeorge Lominadze, MD, MPH, PhD. Dr. Lominadze is a graduate of Tbilisi and Ilia State Medical University in Tbilisi, Georgia.

 

 

Lin-WangLin Wang, MD, PhD. Dr. Wang received his medical degree from Heibei Medical University in Shijiazhuange, Heibei, China, and his PhD from the University of California San Francisco.

 

2017 - 2018 Fellows     

 BeamonAgarwa
Beamon Agarwal, MD, PhD
Hematopathology
 
 Abul Azad
Abul Azad, PhD
Molecular Genetics, ABMGG
 
 Aegean Chan Burnett
Aegean Chan Burnett, MD
Dermatopathology
 
 Mohammad Eskandari
Mohammad Eskandari, MD
Molecular Genetics
 
 Sonali Lanjewar
Sonali Lanjewar, MD
Women’s Health
 
 Patricia Raciti
Patricia Raciti, MD 
Dermatopathology
 
 Gloria Ramos-Rivera
 Gloria Ramos-Rivera, MD
Cytopathology
 
 Saed Sadeghi
Saed Sadeghi, MD
Hematopathology
 
 Sheila Segura
Sheila Segura, MD
Cytopathology
 
 Wei Zhang
Wei Zhang, MD, PhD
GI/Liver
 

Welcome Back!  

  

 Bing HanBing Han, PhD, a post-doctoral fellow in Pathology, Division of Parasitology and Tropical Medicine, has joined the Weiss Laboratory. Dr. Han comes to Einstein from the State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China, where he earned his doctoral degree. He previously trained in the Weiss Laboratory as a visiting student. 

  

Congratulations! 

Newly Minted PhDs  

The following graduate students successfully defended their doctoral theses:

 Nicole AnayannisNicole Anayannis PhD   

Mentor: Michael B. Prystowsky, MD, PhD 

Thesis Topic: “HPV-16 E2 Disruption and E6 and E7 Expression in Relation to Clinical Outcome in Head and Neck Squamous Cell Carcinoma”

 

 Nicole AnayannisIgnacio Guerrero-Ros, PhD 

Mentor:  Fernando Macian-Juan, MD, PhD  

Thesis Topic: “Lipid Challenge Negatively Affects Macroautophagy and Results in Reduced CD4 + T Cell Function” 

 

 Mike VeenstraMike Veenstra, PhD  

Mentor: Joan W. Berman, PhD 

Thesis Topic: “Mechanisms of Viral Seeding and Inflammation of CNS: Potential Therapeutics and Biomarkers for NeuroAIDS”

 

 RamaYakubuRama R. Yakubu, PhD   

Mentor: Louis M. Weiss, MD, MPH 

Thesis Topic: “The Arginine Monomethylome of Toxoplasma gondii and an examination of the role of MAG-1”  

Dr. Yakubu, an MD/PhD candidate, is currently working toward his medical degree at Albert Einstein College of Medicine. 

 

Recent Programs and Events  

Welcome Breakfast for New Residents - July 5   

The five incoming residents received a warm welcome from the Pathology Department’s faculty, residents and staff. Click to view photo. 

  

Residents Farewell Dinner - June 8   

Outgoing residents Evan Himchak, MD; Etan Marks, DO; Lauren McLemore, DO; Gloria Ramos-Rivera, MD; and Elizabeth Stuart Richards, MD, were honored at a festive celebration held at the Westchester Country Club in Rye, NY. Michael Prystowsky, MD, PhD, Professor and University Chair of Pathology at Montefiore and Einstein, congratulated the residents, thanked them for their outstanding dedication and service, and wished them well.  

All five residents were accepted to prestigious fellowship programs: Dr. Himchak in hematopathology (ACGME) at City of Hope Comprehensive Cancer Center, Duarte, CA; Dr. Marks in hematopathology at NYU Langone Health; Dr. McLemore in surgical pathology at MD Anderson Cancer Center, Houston, TX ; Dr. Ramos-Rivera in cytology at Montefiore. Dr. Richards is currently completing a fellowship in gastrointestinal and hepatopathology, University of Washington, Seattle. She will begin a second fellowship in general surgical pathology at Stanford University.  

The Davidoff Society Student Award went to Drs. Evan Himchak, Etan Marks and Gloria Ramos-Rivera, for their outstanding service as chief residents. Dr. Amy S. Fox presented the Resident Research Award to Dr. Marks. 

Pathology Department Annual Retreat 2017 - May 30  

Highlights of this year’s Pathology Department Annual Retreat included a poster session featuring the work of 30 students, post-docs, residents and fellows; oral presentations by predoctoral fellows Alex K. Ray (Mentor: Dr. Bridget Shafit-Zagardo), Rama R. Yakubu (Mentor: Dr. Louis M. Weiss), Matias Jaureguiberry-Bravo (Mentor: Dr. Joan W. Berman) and Mike Veenstra (Mentor: Dr. Joan W. Berman). Keynote speaker Alex Y. Huang, MD, PhD, associate professor of pediatrics, pathology, BME and general medical sciences, Case Western Reserve University School of Medicine, gave an inspiring presentation on “Cdk5 and PD-L1: Modulators of Immune Responses.” Click to view photo gallery.     

See, Test & Treat 2017 - May 13   

Funded by the College of American Pathologists (CAP) Foundation, See, Test & Treat offers uninsured and underinsured women from the Bronx free cancer screenings, onsite test results and referrals to follow up care. The Pathology Department spearheads this annual program at Montefiore in collaboration with the Departments of Radiology and of Obstetrics & Gynecology and Women’s Health. Click to read more and view photos.  

 

 Medical Laboratory Professionals Week 2017 - April 23 - 29   

The Montefiore-Einstein community marked this year’s Medical Laboratory Professionals Week with a series of educational programs and social events. Themed All-Stars Laboratory Team: Teaming Up for Patient Care, activities were held on all campuses to honor the diverse and dedicated group of individuals from the Montefiore-Einstein Pathology Department who staff our medical laboratories. Click to view photo gallery. 

 

 
Click here to log in