We are a driving force of MS research and treatment to stop disease progression, restore function, and end MS forever. The Society is donating $215 million by 2015 to research. Learn more NOW.
Currently the Chapter funds $3.24 million in research programs. These researchers are helping us understand MS, find innovative treatments, and discover a cure. With continued support from donors, the chapter hopes to expand funding to more researchers and projects in our community.
Click on the researcher's name for more details on their project.
Joseph Cantor, Ph.D.
University of California, San Diego
La Jolla, CA
“Targeting integrin signaling in multiple sclerosis” Studying mechanisms that control the ability of immune cells to penetrate the brain, for insights into ways to refine therapies that target those mechanisms.
Michael David, Ph.D.
University of California, San Diego
La Jolla, CA
“Type I interferon suppression of IL-2 production” How interferons reduce relapses in MS, to improve their use and to identify new therapeutic targets.
Thomas E. Lane, Ph.D.
University of California, Irvine
Irvine, CA
“Progenitor cell-induced remyelination following viral infection of the CNS” Exploring cell implantation as a potential therapy for repairing nervous system damage.
Collaborative MS Research Center Award
University of California, Irvine
Pacific South Coast Chapter
A multifaceted effort to explore cell replacement strategies for repairing damage in MS.
Richard Milner, M.D., Ph.D.
The Scripps Research Institute
La Jolla, CA
“Microglial activation by fibronectin and vitronectin in demyelinating disease” Investigating proteins that may induce brain cells to participate in the immune attack and cause damage in MS.
Elizabeth H. Morrison, M.D.
University of California, Irvine/ALSO LARGELY IN WASHINGTON STATE
Orange, CA
“The challenge of giving care to people with MS” Developing a questionnaire for people with MS to evaluate the nature and extent of abuse by caregivers, study risk factors linked to abuse, and estimate its prevalence.
Craig Walsh, Ph.D.
University of California, Irvine
Irvine, CA
“Contribution of the immunoregulatory serine/threonine kinase DRAK2 to EAE” Looking for ways to control the immune system attack in EAE, an animal model of MS.
Jason Weinger, Ph.D.
University of California, Irvine
School of Medicine
Irvine, CA
"Mechanisms of allograft rejection of neural stem cells" Studying a unique method to improve myelin repair in MS-like disease.
Jennifer Welser, Ph.D.
The Scripps Research Institute
La Jolla, CA
“Role of the alpha6 beta4 integrin in astrocyte activation” Testing whether a molecule on brain cells may contribute to a process that hampers tissue repair.
For more information about funding research, contact Karen Barton at (760) 448-8412 or karen.barton@nmss.org.
Local Research Details
Joseph Cantor, Ph.D.
An important early step in the disease course of MS is the movement of inflammatory cells into the brain and spinal cord. One current approach to treating MS targets this movement by blocking “integrins,” one of the adhesion molecules on immune cells that controls their movement into the central nervous system movement. This anti-integrin therapy (natalizumab) has proven to be beneficial, but it would be ideal to target only those immune cells active in MS, leaving the remainder of the immune system intact to fight infection.
In this postdoctoral fellowship, Joseph Cantor, Ph.D., is attempting to target the signaling inside the cell that integrins are responsible for after they adhere. He is using genetically modified mice – missing particular signaling proteins -- to tease out which signaling partners of integrins may be important in MS. If the engineered mice do not develop MS in the same way as normal mice, that will give Dr. Cantor important clues to which signaling proteins to target to improve therapy in people with MS.
Award: Postdoctoral Fellowship
Mentor: Mark H. Ginsberg, MD
Term/Amount: 12/1/2008-11/30/2011; $ 156,515
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Michael David, Ph.D.
Three of the treatments that have been approved by the U.S. Food and Drug Administration to treat multiple sclerosis are interferons, natural forms of which are also produced by human cells in response to viral infection and other stimuli. The exact mechanisms by which interferons help deflect the immune attack launched on the brain and spinal cord in MS are unclear.
Michael David, Ph.D., and colleagues have found that interferons inhibit production of IL-2, a crucial factor in the development of T cells, the major players in the immune attack. Now they are studying human and mouse cells in the laboratory using advanced genetics technology to identify the exact pathway by which interferons may affect IL-2 and hence T cell activity.
Understanding better the mechanisms by which interferons act to reduce relapses in MS could result in improved use of this treatment, yield new molecular markers to predict patient response to therapy, and potentially even identify new therapeutic targets.
Award: Research Grant
Term/Amount: 4/1/07-3/31/11; $455,885
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Thomas E. Lane, Ph.D.
In MS, repeated immune attacks destroy the myelin coating on nerve fibers in the brain and spinal cord, interfering with normal signaling pathways through which the body sends and receives messages. The underlying nerve fibers are also damaged during the course of MS, and many believe that repairing the myelin will help protect them.
Although some natural myelin repair occurs, it is insufficient to keep up with continued assaults. Thomas E. Lane, Ph.D., and colleagues are experimenting with a myelin repair scheme that involves implanting immature myelin-making cells into the brains of mice that have MS-like disease caused by a virus. The team has had initial success in stimulating myelin repair and improving motor skills in these mice. Now they are determining what factors control the movement of the implanted cells into areas of damage and whether the implanted cells are directly responsible for the repair, or simply create an environment that makes natural repair more robust. They also are determining whether reducing the immune disease activity helps or hinders myelin repair.
Results of each aim of this project should inform future strategies for repairing myelin in people who have MS.
Award: Research Grant
Term/Amount: 4/1/07-3/31/10; $495,551
Funded in part by a gift from the Alan Buegeleisen Research Fund
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Collaborative MS Research Center Award
Principal Investigator:
Thomas E. Lane, Ph.D., Professor, Molecular Biology & Biochemistry
Collaborators at UC Irvine:
George Chandy, M.D., Ph.D.
Michael Demetriou, M.D., Ph.D.
Steven S. Schreiber, M.D.
Michael Cahalan, Ph.D.
Hans S. Keirstead, Ph.D.
Dr. Thomas E. Lane is a Chancellor’s Professor in the Department of Molecular Biology & Biochemistry at the University of California, Irvine. He has extensive experience in animal models of both the nervous and immune systems. Dr. Lane earned a Bachelor of Science degree in microbiology at Ball State University in Muncie, Indiana, and a Ph.D. in microbiology and immunology from the University of California, Los Angeles. He completed a postdoctoral fellowship in virology, funded by the National MS Society, at Scripps Clinic in La Jolla. Dr. Lane has published some 75 scientific papers and currently serves as a peer reviewer for the Society’s research programs department.
Multiple sclerosis occurs when the immune system attacks and damages nerve fiber-ensheathing myelin and nerve fibers themselves. The promise of cell-replacement strategies to treat MS is significant: Imagine being able to infuse people with cells that could make new myelin, or transform into healthy nerve cells. But introducing new cells into humans also involves great risk. Developing safe and effective cellular therapies is a matter that demands tremendous focus.
This is the goal of the new Collaborative MS Research Center Award to Thomas E. Lane, Ph.D., at the University of California, Irvine. Dr. Lane’s team is investigating how to combine surgical implantation of immature cells with modulation of the immune attack – thus simultaneously promoting myelin repair while muting myelin damage.
Dr. Lane has extensive experience in animal models of both nerve cell loss/repair and T cell immunology, both areas that are extremely relevant to MS research. Recently he has also examined cell-replacement strategies for promoting myelin repair.
Dr. Lane is leading a project seeking to define key “chemokine receptors,” or messenger receivers that allow for migration of immature myelin-making cells (also known as oligodendrocyte progenitors, or OPCs) following transplantation into mice with established damage to myelin. Chemokines are immune chemicals that attract and assist the migration of the principle culprits of the immune attack in MS – T cells and macrophages – into the brain and spinal cord. Dr. Lane has previously been funded by the Society to study these chemicals and their receptors, or docking sites, for clues to stopping the influx of immune cells into the brain and spinal cord, but now is looking at them as possible vehicles for allowing the migration of therapeutic cells.
Dr. K. George Chandy is a professor in the department of physiology & biophysics, who pioneered the study of ion channels in the immune system. Ion channels are tiny pores on the surface of immune T cells that control the influx of charged particles and allow T cells to become activated. The project he is conducting in this collaboration focuses on mice with an MS-like disease called EAE. Dr. Chandy is evaluating the therapeutic potential of implanting OPCs while administering ion-channel blockers, which may turn down the immune attack while the cells go about the business of repair.
Dr. Michael Cahalan, professor and chair of the department of physiology & biophysics, is new to MS, but is also a pioneer in the study of ion channels and their function in the immune system. He is developing novel methods for tracking and visualizing the migration of stem and immune cells within the living nervous system.
Dr. Michael Demetriou is director of the Comprehensive MS Program, and has broad experience in T cell biology in MS and EAE. In this collaboration, Dr. Demetriou is investigating enzymes that exist on the surface of T cells and help to form carbohydrate molecules, and how such enzymes direct T cells. He is looking for clues to suppressing the damage that T cells incur in mice with EAE, and also is looking at a role these enzymes might play in directing transplanted OPCs.
Dr. Steven Schreiber is professor and chair of the department of neurology. His laboratory was the first to demonstrate activation of p53, a major regulator of cell death, in degenerating nerve cells. He brings this expertise to the field of MS research by examining how nicotinamide – which may inhibit p53 – may increase the repair capacity of nerve stem cells transplanted into mice with EAE.
These studies require major resources, in terms of cell populations for transplantation and imaging techniques. Collaborator Dr. Hans Keirstead, an associate professor of anatomy and neurobiology with extensive expertise in generating stem cell lines, is providing the cells that are proposed for these studies.
These projects cover the broad spectrum of efforts necessary to ensure the continued development of safe and effective cell-based strategies for treating people with MS.
Term/Amount: 11/1/09-10/31/14; $742,500
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Richard Milner, M.D., Ph.D.
Early in the MS-causing immune response, the “blood-brain barrier” (BBB) that normally is highly selective about what gets into the brain from the bloodstream breaks down, allowing immune cells to invade. Once inside the brain, these cells initiate an immune attack that destroys nerve-insulating myelin and myelin-producing cells called oligodendrocytes.
Richard Milner, M.D., Ph.D., proposes that the breakdown of the BBB leaves deposits of two proteins called fibronectin and vitronectin in the brain. The presence of these proteins may in turn stimulate specialized brain cells called microglia. Normally “quiet,” brain microglia activated by the presence of these proteins release chemicals that are toxic to oligodendrocytes. In this project, Dr. Milner is confirming that fibronectin and vitronectin can indeed activate microglia in cells grown in the lab. He is also investigating if these proteins promote microglial activation and subsequent oligodendrocyte destruction in a mouse model of MS.
Suppressing the activation of microglia may help promote oligodendrocyte survival and could lead to the replacement of myelin lost in the MS disease process.
Award: Harry Weaver Neuroscience Scholar
Term/Amount: 8/1/06-7/31/11; $626,997
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Elizabeth H. Morrison, M.D.
Dr. Elizabeth Morrison is a respected and dedicated family physician-educator who specializes in the treatment of people with MS. She earned a B.A. in psychology and medical degree from Brown University. Her internship and residency were in family medicine, and also earned a Master’s degree in medical education from the University of Southern California. Dr. Morrison did a special MS fellowship later in her career and is now an MS specialist physician practicing at the LA County-USC MS Center. She is also associate professor family medicine at the UCI School of Medicine and voluntary associate professor of neurology at the USC-Keck School of Medicine. Dr. Morrison has conducted and published numerous research studies since joining the UCI faculty in 1998, including research on exercise in MS, and has collaborated with the UCI Program in Geriatrics on disability projects.
A National MS Society-funded study in Massachusetts suggested that abuse may be a more significant problem in MS than previously suspected. Little is known concerning the frequency and types of abuse of persons with MS or the characteristics of abusers. Better information about abuse and MS could help to design programs for the prevention of abuse and improve our ability to identify abuse when it does occur.
Elizabeth Morrison, M.D., MSEd, and colleagues are investigating caregiver mistreatment of people with MS. They are first developing operational definitions of the five major categories of mistreatment (physical abuse, psychological abuse, sexual abuse, neglect, and financial exploitation) and testing a new questionnaire that can reliably determine whether – and how severely – a person with MS may be experiencing these types of mistreatment. They also are determining what risk factors are associated with abuse and neglect among people with MS and their caregivers. Last, they are estimating how many people with MS across the country are being abused or neglected.
These results will enable better detection and prevention of caregiver mistreatment of people with MS.
Award: Health Care Delivery and Policy Research Contract
Term/Amount: 7/1/09-6/30/11; $296,940
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Craig Walsh, Ph.D.
Dr. Craig M. Walsh is a respected immunologist who has a track record in the study of cancer. This project would be his first supported by the National MS Society. He earned his undergraduate and Ph.D. degrees at the University of California, Los Angeles and conducted postdoctoral research in immunology at UC San Diego. He is now Associate Professor in the department of Molecular Biology and Biochemistry at UC Irvine. Dr. Walsh has served as a peer reviewer for the NIH, is on the editorial board of the journal Autoimmunity, and is Associate Editor of the Journal of Immunology.
The immune system ordinarily protects the body from injury by infectious agents, such as viruses or bacteria. Immune system cells coordinate what to attack and how to attack it using a complex network of molecules. Some of these "immuno-regulatory" molecules increase the activity of the immune system, while others suppress its activity. If the delicate balance between activation and suppression is flawed, one result may be an immune system attack against a part of the body – in the case of MS, the target is the myelin that surrounds and protects nerve fibers in the brain and spinal cord.
In this research project, Craig Walsh, Ph.D., will investigate the role of one regulatory molecule, known as DRAK2, in lab mice with EAE, a disease with similarities to MS. The DRAK2 protein molecule is one that regulates the activity of the important immune system T cells. By engineering changes in the gene that codes for the protein, Dr. Walsh will determine how DRAK2 influences the T cells that attack myelin. The results of this work may lead to ways to treat MS by controlling the specific immune T cells that launch the attack on myelin in people.
Award: Research Grant
Term/Amount: 11/1/09-10/31/12: $ 435,619
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Jason Weinger, Ph.D.
Jason Weinger, Ph.D., is a Postdoctoral Fellow in the Department of Molecular Biology and Biochemistry at the University of California, Irvine. His mentor is Thomas E. Lane, Ph.D., a leading scientist in MS and stem cell research. Dr. Weinger earned his Ph.D. in neuropathology at Albert Einstein College of Medicine and also completed a postdoctoral fellowship there. His work on signaling in the central nervous system has led to two papers published in high profile journals. Dr. Weinger’s long-term goal is to investigate the mechanisms involved in promoting myelin repair through stem cell transplantation.
In MS, the immune system attacks and damages myelin, the protective coating of nerve fibers in the brain and spinal cord. Nerve fibers are damaged as well. Evidence from mouse models indicates that neural stem cells (NSCs, or immature nerve cells) can repair damaged myelin when injected into mice with MS-like disease. Small clinical trials are underway, or in the planning stages, to start investigating this concept in people with MS and related diseases.
Jason Weinger, Ph.D., is looking at ways to prevent the immune system from recognizing NSCs as foreign. Working with mice that have a disease similar to MS, he is investigating whether immune system stem cells from a source closely related to the NSC donor can trick the immune system into ignoring the foreign NSCs, which will then be able to repair damaged myelin.
This research could lead to new ways to repair damaged myelin and restore function in people who have MS.
Award: Postdoctoral Fellowship
Mentor: Thomas E. Lane, PhD
Term/Amount: 7/1/11-6/30/14; $150,800
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Jennifer Welser, Ph.D.
Dr.Jennifer Welser completed her Ph.D. in Cellular and Molecular Pharmacology and Physiology at the University of Reno, Nevada. She has completed a postdoctoral fellowship there as well, focusing on molecules known as integrins and their role in muscular dystrophy. Her highly productive doctoral training included three publications in which she was the first author. Dr. Welser also received the university’s George C. Bierkamper Outstanding Graduate Student Award in Pharmacology, which is presented to the student who demonstrates the highest level of excellence in academics and research. Dr. Welser is now studying the role of integrins in MS at The Scripps Research Institute in La Jolla with Dr. Richard Milner, a noted expert in integrins and MS. Her ultimate goal is to reveal new information about the underlying mechanisms that lead to MS.
Multiple sclerosis occurs when immune cells attack the brain and spinal cord, damaging the nerve fiber sheaths (myelin) and nerve fibers in the brain. Normally, the blood-brain barrier (BBB) acts as a shield to protect the brain from potentially harmful constituents of the blood. Astrocytes are the most abundant cells in the brain. They are involved in the formation and maintenance of the BBB and provide protective effects during injury to the brain by becoming activated in a process known as reactive gliosis. Recent studies however suggest that reactive gliosis may prevent repair of the brain and may contribute to MS progression.
Dr. Welser is testing the idea that alpha6 beta4 integrin (an adhesion molecule expressed by astrocytes) may contribute to reactive gliosis. She is studying the function of this molecule both during mouse development and in a mouse disease model of MS called EAE.
As astrocytes are the only cell type in the brain that express the alpha6 beta4 integrin, this integrin may represent a promising therapeutic target for stopping MS.
Award: Postdoctoral Fellowship
Term/Amount: 7/1/10-6/30/13; $ 150,800
Funded in part by the Dave Tomlinson Research Fund through the NMSS Mid-America Chapter
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