Vel-Earl Grande-V Richard Zerling Laboratory
Treatment of stroke using endogenous or exogenous stem cells
The Earl Grande, Vel, V. Richard Zarling Stroke, Stem Cell, and Neuroimaging Laboratory is focused on identifying novel treatments for stroke using endogenous (originating or growing within an organism or tissue) or exogenous (originating outside an organism or system) stem cells. Stroke remains the second leading cause of death in the United States. Approximately 650,000 people suffer a stroke each year. Despite great advancements in medical technology, less than 5% of patients receive any form of treatment. Consequently, 30% of patients die and 30% have significant, permanent disability.
In our laboratory, we focus on finding treatments for patients who progress to having a completed stroke and permanent disability. We believe that this is an opportune time, given recent discoveries of stem cells in the adult brain and even more recent discoveries involving cell reprogramming where now your own skin cells can be converted into stem cells or directly into neurons that can be used for transplantation.
Our research is focused on three specific aims:
- Identifying normal neurogenesis (formation and development of nerve cells) in the adult brain and studying ways to manipulate and enhance this normal production of neurons
- Using exogenous stem cells (transplantation) delivered either through a microcatheter within the arteries of the brain, or injected intravenously or directly to the area of a stroke
- Reprogramming resident brain cells to generate neurons that can incorporate into the existing circuitry of the brain following a stroke.
Through collaborations with the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota, we are studying new imaging models focused on stroke, cerebral vascular reserve, and the study of cranial nerves found at the skull base.
Normal Adult Neurogenesis
The discovery of neural stem cells (NSCs) in the adult mammalian brain, including humans, has raised the intriguing possibility of using endogenous NSCs for regeneration and repair of damaged brains. Specifically, endogenous NSCs have been found in the subventricular zone (SVZ) and the dentate gyrus (DG).
Exogenous Cell Transplantation and Cell Reprogramming
Together with Dr. Walter Low, we are studying the potential use of human non-hematopoietic cord blood stem cells found in bone marrow (nh-UCBSCs) for the treatment of stroke.
The Center for Magnetic Resonance Research (CMRR) located at the University of Minnesota is a world renowned MRI research facility. Known for its pioneering work in ultra high-field MRI, the facility produced the world's first human-compatible 7-tesla scanner in 1999.
Nakafuku M, Grande A, Neurogenesis in the damaged mammalian brain, In: Comprehensive Developmental Neuroscience, Chapter 74. Eds. Pasko Rakic and John Rubenstein. Elsevier Inc (Amsterdam) (2011).
Nakafuku M, Nagao M, Grande A, Cancelliere A, Revisiting neural stem cell identity, Proceedings of the National Academy of Sciences 105(3): 829-830 (2008).
Nan Z, Grande A, Sanberg C, Sanberg P, Low W, Infusion of human umbilical cord blood ameliorates neurologic deficits in rats with hemorrhagic brain injury, Annals of the New York Acadamy of Sciences 1049:84-96 (2005).
Rodrigues C, Spellman S, Sola S, Grande A, Cheryle L, Low W, Steer C, Neuroprotection by bile acid in an acute stroke model of rat, Journal of Cerebral Blood Flow & Metabolism 22: 463-471 (2002).
Dr. Andrew Grande holds out hope for children who have had a stroke in-utero because of research in neuroplasticity – a rewiring of the brain.
Nan (Crusoe) Zhenhong, M.D., currently a scientist at the University of Michigan
Mario Julian - currently a medical student at the New York Medical College
"I am an Interventional Neuroradiologist with a background in neuroradiology and nuclear medicine. I went to medical School in India and also completed a Nuclear Medicine Residency there from the All India Institute of Medical Sciences in New Delhi. Thereafter, I moved to the USA and spent a year on MRI and PET research in children with epilepsy. I then moved on to finish a residency in Radiology at the University of Minnesota, followed by fellowships in Neuroradiology and Endovascular Surgical Neuroradiology at Washington University in St. Louis. I love my clinical practice, and the great team of fellow physicians with whom I work. On the clinical side, I like to treat children with complex neurovascular conditions, and find that the most fulfilling aspect of my job along with the opportunity to team up with other interventionalists and cardiologists in arriving at solutions for some of the complex vascular problems our patents present with at the University of Minnesota and HCMC. I love teaching neuroanatomy and MRI principles. My wife and I enjoy living in the Twin Cities and look forward to our one-year-old son growing up here!"
- Pathophysiology of cerebral aneurysms and AVMs with a particular interest in the role of neurovascular anatomy and biomechanics in causing these lesions to bleed
- The role of inflamation in stroke and traumatic brain injury, and imaging inflammation in these conditions
- The role of the spleen in immunomodulatiom of the response to stroke and head injury
- Balloon assisted embolization techniques
- Stem cells in stroke
- Device development
- Transcranial magnetic stimulation.
Hobbies: Travel; reading about history and all kinds of funky mathematics; writing; intermittent attempts at working out; linguistics and archeology.
Joined the lab: 2011
"I'm from Saudi Arabia, 32 years old and married. I have two children. My wife is a nurse who is applying for a Ph.D. at the U of M. I did my undergraduate studies in medical technology and then I went to graduate school in medicine, still doing my neurosurgery residency. Currently, I'm a postdoctoral research associate fellow in neuronal stem cell at the Neurosurgery Department. I'm also pursuing my executive master's in Healthcare Administration at the U."
Research Interests: direct reprogramming of astrocytes to neurons using retrovirus packaging specific transcription factors and injecting them into canine and non-human primate stroke models; fiber tract neuroimaging and dissecting.
Hobbies: traveling, sky diving, scuba diving, fishing, swimming, climbing, hiking, river rafting, and archery.
Joined the lab: 2011
“Many of my personality traits were acquired during the 12 years I was a gymnast as a child. Gymnastics is an extremely dynamic sport with a steep learning curve, and endless opportunities for challenging oneself to new skill levels. I have always been excited by the endless possibilities and new things to learn in medicine. I am excited to be a lifelong learner and have constant challenges in front of me. I have also been struck by the need for physicians in developing and third world countries as I have visited them. I believe we are just beginning to bridge this healthcare gap in effective ways, even though people have been practicing charitable medicine for years. I want to be part of developing sustainable healthcare communities that will eventually be able to stand on their own and employ local residents.”
- Azusa Pacific University, B.S.
- University of Minnesota Medical School, M.D. [Expected 2015]
Research Interests: Sustainable global health practice, stem cell therapy, and organ transplant
Hobbies: Running, singing & dancing, photography, and traveling
Joined the Lab: Fall 2011
“Medicine is a field dedicated to promoting and restoring health. It is this fundamental element that attracted me to it in the first place. Neurosurgery in particular interests me because presently we are at the foot of a rapid ascent towards great gains in knowledge and understanding in neuroscience. Thanks to an explosion of interest, innovation, and research effort, the next decade and thereafter will surely bring untold insights into the way the brain works. I want to make it my life's work to be a part of this "neuroscience revolution" by dedicating myself to translational research and application thereof in the context of patient care.”
- Carleton College, B.A.
- University of Minnesota Medical School, M.D. [Expect 2014]
Research Interests: Animal models of cerebrovascular disease, trigeminal neuralgia, intranasal treatment of Alzheimer's disease, and technology advances in neurosurgery
Hobbies: Tennis, fitness, and aquatic sports
Joined the Lab: Fall 2011
"As a young child I had a bump in my leg which the doctors thought was cancer. As a 15 year old, I was old enough to recognize the implications of this and was able to research it on the internet. I was so afraid. The doctor was able to ease my anxiety just by talking and listening to me. In the end it was nothing, but that experience convinced me that I want to help people in the same way the physicians helped me. Since then I have been drawn to medicine and the special gift that physicians can give to their patients. As an undergraduate working in the laboratory, I am closer to my goal of one day working with patients. The translational work in this laboratory bridges the gap between basic science and the altruistic side of helping patients."
- Hopkins High School
- University of Minnesota - Twin Cities, B.S. [Expect 2015]
Research Interests: Neural stem cells, neuroanatomy, gamma-knife radiation for treatment of brain tumors
Hobbies: Running, boating, and traveling
Joined the Lab: Fall 2011
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