Faculty Profile: Conrad Johanson, PhD

Conrad Johanson
Conrad Johanson, PhD
Professor Emeritus of Neurosurgery
Neurosurgery
Work: +1 401-885-2231
Alpert Medical School Professor of Neurosurgery, Conrad Johanson, investigates molecular and physiologic aspects of transporter mechanisms at the blood-brain-cerebrospinal fluid (CSF) interfaces that actively create an optimal chemical environment for neuronal functioning. In brain diseases and fluid disorders, pharmacologic remedies are needed to correct distortions in choroid plexus-CSF neurochemistry, in order to overcome cognitive deficits and other neural dysfunctions. Research goal: To restore CSF biochemical composition (homeostasis) and fluid dynamics disrupted by central nervous system pathology. Preserving a functional CSF circulation throughout aging helps to maintain cerebral metabolism, neurotransmission and sound cognition.

Biography

Conrad Johanson, Professor Emeritus of Neurosurgery, investigates the roles of the choroid plexus-CSF nexus and blood-brain barrier (capillaries) in regulating cerebrospinal fluid composition for neurons. His NIH-funded research over the past three decades, that has included models of ontogeny, hydrocephalus, ischemia and aging, has culminated in more than a hundred publications. These projects have clarified how CSF and interstitial fluid homeostatic mechanisms, including periventricular neurogenesis, undergo gene expression changes in fetal brain development, hydrocephalus, senescence and Alzheimer's disease. Translational goal: To sustain the homeostatic capabilities of CSF in order to prevent cognitive losses as the brain weakens with aging. As Director of the Cerebrospinal Fluid Laboratory in Neurosurgery at Rhode Island Hospital, he has developed pharmacologic strategies to prevent/repair damage to the 'barrier cells' that stabilize neurochemistry and fluid dynamics.

Dr. Johanson was awarded the international Pudenz Prize in 2005 for career excellence in CSF physiology and molecular research. More than sixty biomedical Society presentations from the Johanson laboratory, delineating the protective and trophic roles of the CSF for neuronal networks, have been presented at international meetings and symposia in Europe, Asia and South America. His current scientific advisory work for NASA analyzes CSF pressure and brain fluid reabsorption changes in U.S. astronauts during and after space flight. The NASA project aims to stabilize astronaut brain and eye functions inflight so that long space missions will become feasible.

Before joining the Brown University faculty in the Research Scholar Track, Professor Johanson received tenure at the University of Utah, Department of Pharmacology, teaching medical and graduate-level pharmacology, mentoring PhD students, and administering an NIH-sponsored doctoral training grant. At the School of Medicine in Salt Lake City he was also associate professor of Anesthesiology, collaborating on blood-brain barrier projects. At the inception of the Department of Clinical Neurosciences at Brown in 1985, Dr. Johanson was recruited as director of research for the Program in Neurosurgery. Over the past 25 years as professor of neurosurgery, his academic and professional activities have included training students and fellows for independent studies, honors theses, graduate degrees and post-doctoral stints; editing and reviewing for forty archival scientific journals; and serving on grant study sections for NIH, NSBRI and NASA.

Institutions

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Research Description

Neuropeptide hormones, growth factors and neurotrophic agents, secreted by choroid plexus into cerebrospinal fluid (CSF), play a key role in regulating the neuronal fluid environment: its pressure, volume and composition. Conrad Johanson has received multiple R01 grants from NIH to study these peptide-mediated regulatory processes. Such peptide/protein modulators in CSF play a key role in driving fetal brain development, by regulating neurogenesis and gliogenesis in the subventricular zone. They also mediate homeostatic control of brain water content, CSF formation rate, and blood-brain barrier permeability in healthy young adults. The CSF Laboratory also analyzes these homeostatic processes in late life when the CNS is stressed by ischemia, trauma and inflammation. Overall, these peptide/protein regulators in choroid plexus-CSF are up- or down-regulated in order to facilitate brain adjustments to the stressful stimuli encountered in disease or injury.

The Johanson laboratory and colleagues study how the immature, healthy adult and aging central nervous systems react to the stressors of arterial hypertension, reduced blood flow and cerebrospinal fluid formation, elevated intracranial pressure, traumatic brain injury, dehydration, and hyperthermia. The choroid plexus-cerebrospinal fluid (CSF) nexus has a pivotal role in regulating the composition and volume of the brain extracellular fluid, i.e., the microenvironment of neurons. His research team delineates mechanisms of CSF homeostasis and how these transport and distributional phenomena are altered in various pathological states: forebrain ischemia, hydrocephalus, and Alzheimer's disease. The operative working hypothesis is that perturbations and dwindling of the CSF dynamics (reduced CSF turnover) lead to or exacerbate dementia states. Reduced clearance of the beta-amyloid peptide from the CNS, for example, due to attenuated CSF formation and reabsorption, can cause neurotoxicity and destabilize brain metabolism and blood flow.

Models of rats and transgenic mice are being used to provide insight on how fluid balance mechanisms and solute transport at the blood-CSF barrier (choroidal epithelium) and ependyma (brain-CSF boundary) are integrated with corresponding phenomena at the blood-brain barrier interface (cerebral endothelium and astrocytes). The translational goals are to develop agents and regimens that will repair/strengthen the regulatory 'barrier cells' in the choroid plexuses and in the neurovascular unit: endothelial cells, astroglia, pericytes and neurons. By therapeutically stabilizing the choroid plexus and cerebral microvessels in aging and early disease states, e.g., mild cognitive deficit and normal pressure hydrocephalus, it should be feasible eventually to extend neuroprotection and neuroregeneration to the latest periods of the human lifespan.

Grants and Awards

Recipient of Tenure Award, Department of Pharmacology, University of Utah School of Medicine, 1981
Frontiers of Science and Technology, Marquis Who's Who, Inc., 2nd ed., 1985
Distinguished Alumnus Award for Professional Achievement, E. Nazarene College, Quincy, MA, 2001
Fellow, International Society for Complexity, Information and Design, Princeton, NJ, 2002
Distinguished Alumnus Award, Lexington Christian Academy, Lexington, MA, 2005
Recipient of the Robert Pudenz Award for Excellence in CSF and Hydrocephalus Research, 2005

Affiliations

Society for Neuroscience
American Physiological Society
American Society for Pharmacology and Experimental Therapeutics
International Society for Developmental Neuroscience
International Society for Cerebral Blood Flow and Metabolism
American Society for Neurochemistry
Society for Research on Hydrocephalus and Spina Bifida
Global College of Neuroprotection and Neuroregeneration

Funded Research

National Institutes of Health (NIH):

Research Career Development Award, National Institute of Neurological and Communicative Disorders and Stroke (NINDS), 1977-1982

Ontogeny of Homeostatic Transport in Choroid Plexus, NINDS R01 Research Grant, C.E. Johanson, Principal Investigator, 1977-1980

Maturation of CSF Secretory Mechanisms, NINDS R01 Research Grant, C.E. Johanson, Principal Investigator, 1980-1983

Acid-Base Transporters and pH in the Immature CNS, NINDS R01 Research Grant, C.E. Johanson, Principal Investigator, 1983-1986

Development of Choroid Plexus-CSF Transport Systems, NIH NINCDS RO1 Research Grant, C.E. Johanson, Principal Investigator, 1989-1995

Choroid Plexus, Growth Factors, Aging and Injury. NIH NINDS RO1 Research Grant, C.E. Johanson, Principal Investigator, 1995-1999

Peptide Regulation of the Choroid Plexus-CSF System. NIH NINDS RO1, C.E. Johanson, Principal Investigator, 1999-2004

Age-Related Decrease in A-Beta Peptide Clearance Pathways: CSF and BBB, C.E. Johanson, Principal Investigator, NIH NIA R01 Research Grant, 2006-2010.

Research Training in Pharmacological Sciences, NIH Training Grant, research supervisor, 1974-1984

Neuropharmacology and Neurochemistry Program Project, research instructor, 1973-1975

Training Grant for Post-Clinical Anesthesia Training, National Institutes of Health, research advisor, 1980-1985

Pathophysiological Responses to Injury, NIH, National Institute of General Medical Sciences, Institutional Postdoctoral NRSA (T32) M. Epstein, Principal Investigator; C.E. Johanson, Co-Principal Investigator, 1990-1992

Trauma, Sepsis and Inflammation National Institute of General Medical Sciences Trauma Training Grant, I. Chaudry, Principal Investigator, C. Johanson, research supervisor, 1999-2002

Trauma and Inflammation Research Training Grant, National Institute of General Medical Sciences Trauma Training Grant, J. Albina, Principal Investigator, C. Johanson, research supervisor, 2004-2014

Alzheimer's Disease Clinical Center, Neuropathology Core, National Institute on Aging, E. Stopa., Principal Investigator and C. Johanson, Co-investigator, pending.

Agrin, Amyloid and Alzheimer's Disease, Veterans Administration, C. Johanson, Principal Investigator and E. Stopa, co-investigator, pending.

Apolipoprotein E, Amyloid-beta and Blood-Brain Barrier Permeability, K08, National Institutes of Health, J. Donahue, Principal Investigator, and C. Johanson, mentor, 2006-9

National Science Foundation:

Multi-User Equipment Grant, National Science Foundation, 1979-1980

Private Foundations:

Biochemical Control of CSF Production, March of Dimes Foundation, M. Epstein and C. Johanson, Co- Principal Investigator, 1985-1988

Effect of Phenytoin on the Transport and Distribution of Sodium and Potassium between Various Compartments in the Central Nervous System, Epilepsy Foundation of America, C. Johanson, Principal Investigator, 1975-1976

Microdialysis of Cerebrospinal Fluid from the Cisterna Magna. Grass Foundation, C.E. Johanson, Principal Investigator, 1990-1993

Serotonin Effects on Chloride Transport by Choroid Plexus, Grass Foundation, C.E. Johanson, Principal Investigator, 1994

Cystatin C and TUNEL Immunostaining in Spinal Cord in Amyotrophic Lateral Sclerosis, George Robinson Foundation, C.E. Johanson, Principal Investigator, 1996-1997

Growth-factor Induced Hydrocephalus in a Transgenic Alzheimer Mouse Model, Alzheimer's Association, C. Johanson and E. Stopa, co-principal investigators, 2004-2007

Biomarkers for Drug Targeting in Alzheimer's Disease, American Health Assistance Foundation, A. Baird, Principal Investigator, and C. Johanson, Co- Principal Investigator, pending.

Corporations:

Minimally-Invasive and Metabolic Models of Hydrocephalus, Medtronic Neurologic Technologies, C. Johanson and J. Duncan, co-principal investigators, 2006-2009.

Local Funding Sources:

Protection of the pH of the Extracellular Fluid of the Brain during Systemic Metabolic and Respiratory Acidosis: The Role of the Choroid Plexus, C. Johanson, Principal Investigator, Dean's Research Fund, University of Utah, 1976-1977

Physiological Characteristics of the Cerebrospinal Fluid Secretory Process, C. Johanson, Principal Investigator, Dean's Research Fund, University of Utah, 1974-1975

Immunohistochemical Analyses of ALS Brains, Brown University UTRA collaborative study with Jinn-Wien Teng, 1998.

Teaching Experience

University of Kansas (1968-1970):

Physiology 270: Graduate renal physiology

Physiology 271: Graduate cardiovascular and CNS physiology

University of Utah (1971-1985):

Pharmacology 601-602-603: Sophomore medical pharmacology

Pharmacology 791: Pharmacokinetics

Pharmacology 727: Neurochemistry

Pharmacology 721: Acid-base and electrolytes

Pharmacology Summer Courses (e.g., Food and Drug Administration pharmacology)

Brown University:

Basic Neuroscience Course (Program in Neurosurgery)

Cell Volume Regulation Seminar (Physiology Department)

Advanced Physiology BI 208: Peptides and Growth Factors