Daniel Lowenstein, MD

Executive Vice Chancellor and Provost
(EVCP)
+1 415 476-4451

Dr. Daniel H. Lowenstein is the Executive Vice Chancellor and Provost at the University of California, San Francisco (UCSF), the Robert B. and Ellinor Aird Professor and Vice Chairman in the Department of Neurology at the University of California, San Francisco (UCSF), and Director of Physician-Scientist and Education Training Programs for the UCSF School of Medicine.

Dr. Lowenstein received his B.A. degree in Mathematics from the University of Colorado in 1973, an M.S. degree in Man-Environment Relations from The Pennsylvania State University in 1978, and an M.D. degree from Harvard Medical School in 1983. Following an internship in Pediatrics at UCSF in 1983-84, he completed his residency in Neurology at UCSF from 1984-87, serving as Chief Resident in the final year. He then did a two-year fellowship in Stanley Prusiner's Laboratory, investigating the sequence homology of the PrP gene in various rodent species. He went on to become a faculty member in the Department of Neurology at UCSF, established the UCSF Epilepsy Research Laboratory, and became the Robert B. and Ellinor Aird Professor of Neurology from 1998-2000. He then joined Harvard Medical School (HMS) as the Dean for Medical Education for two and a half years, overseeing a re-organization of curricular governance, the creation of a new educational technology program, the establishment of the HMS Academy (a novel structure for the support of the school’s education mission), and the initial planning for a major revision of the curriculum. In 2003, for family reasons, he moved back to UCSF in his current position.

Dr. Lowenstein is a clinician-scientist who studies both basic science and clinical aspects of epilepsy. His laboratory studies (carried out from 1989 to 2002) have addressed the fundamental mechanisms of neuronal network remodeling that occur during epileptogenesis; i.e. the process in which a normal network transforms into a hyperexcitable network capable of producing or relaying seizure activity. The main efforts of his research group focused on the various forms of cellular reorganization that are observed in humans with temporal lobe epilepsy, and the parallels between reorganization in the adult nervous system and normal developmental processes. Important findings by his team included the discovery that seizure activity in an adult model of temporal lobe epilepsy causes a marked increase in the birth of hippocampal neurons, and the recognition that numerous molecules responsible for normal development are also expressed in this same brain region in the adult. These studies bear not only on the neurobiology of epilepsy, but also on the broader issue of neurodevelopment and the capacity for regeneration in the adult nervous system after injury.

In 2002, Dr. Lowenstein turned his attention toward questions related to the genetic basis of common forms of human epilepsy. Working with colleagues from throughout the world, he helped create the Epilepsy Phenome/Genome Project (EPGP), an international, multi-institutional, collaborative study that is collecting detailed phenotype date on 5,250 subjects with specific forms of epilepsy, with the aim of determining the genetic determinants of their disease with whole exome and whole genome sequencing. Having completed the sixth year of the project, EPGP has enrolled more than 4,000 participants and has compiled the most extensive and detailed phenotype dataset in the history of epilepsy research. In 2011, Dr. Lowenstein and colleagues were successful in receiving funding for a new NINDS Epilepsy Center Without Walls entitled “Epi4K: Gene Discovery in 4,000 Epilepsy Genomes”, which has as one of its goals the analysis of the EPGP cohorts. This joint work of EPGP and Epi4K has already yielded major new insights into the genetic basis of the epileptic encephalopathies, a particularly devastating form of epilepsy.

Dr. Lowenstein's main clinical research to date has been on the management and treatment of patients with status epilepticus; i.e. unusually prolonged seizures. He was the Principal Investigator of a prospective, multi-centered, NINDS-sponsored clinical trial looking at the potential benefits of active treatment of patients in status epilepticus in the pre-hospital setting. This five-year study, completed in 1999, helped define the optimal therapy for these patients nationally. Dr, Lowenstein currently serves as Co-Principal Investigator and member of the Neurological Emergency Treatment Trials (NETT) Clinical Coordinating Center, which oversees a network of academic centers and affiliated hospitals in the U.S. carrying out numerous clinical trials related to acute neurological disease. As part of this effort, he was Co-Principal Investigator with Dr. Robert Silbergleit for the recently completed Rapid Anticonvulsant Medications Prior to Arrival Trial (RAMPART) study, which successfully demonstrated the utility of intramuscular benzodiazepine treatment of status epilepticus in the pre-hospital setting. RAMPART was selected as the “2013 Clinical Trial of the Year” by the Society for Clinical Trials.

Dr. Lowenstein’s efforts in epilepsy research were recognized by the American Epilepsy Society’s 2001 Basic Research Award, an honor given each year to the foremost basic science investigator whose research “contributes importantly to understanding and conquering epilepsy.” He also served as president of the American Epilepsy Society in 2003-04, and was selected as the 2012 recipient of the Lennox Award, given to “a clinician-scientist who is felt to be among the most outstanding investigators in the field of epilepsy research." This year, he received an Ambassador Award from the International League Against Epilepsy (ILAE) “in recognition of outstanding international contributions to the cause of epilepsy.” He was also recently appointed as Chair of the ILAE Genetics Commission for the next four years.

Dr. Lowenstein has also been actively involved in defining scientific policy at the national level, having served a 4-year term as a member of the Advisory Council of the National Institute of Neurological Disorders and Stroke (NINDS) and Chair of the NINDS Clinical Trials Subcommittee from 2000-2004. He has also been the Chair of the NINDS Epilepsy Benchmarks Committee since its inception in 2000, and Chair of the NINDS Epilepsy Common Date Elements (CDE) Committee since its formation in 2008.

In addition to his research interests, Dr. Lowenstein is an avid and highly-regarded teacher, and he has had an active role at UCSF concerning issues related to cultural diversity and civil rights. In recognition of his leadership at UCSF in these areas, as well as his long-standing advocacy for students, staff and faculty of all backgrounds, he received the 1998 Black Student Health Association’s Faculty Award, the 1998 UCSF Dr. Martin Luther King, Jr. Award, the 2006 Holly Smith Award for Exceptional Service to the UCSF School of Medicine, the 2009 UCSF Chancellor’s Award for Public Service, and the 2015 UCSF Chancellor’s Award for Disability Services. In 2013, he was selected by the UCSF community to deliver “The Last Lecture” (see: http://youtu.be/ymAlnYRuBOA).

Regarding his teaching accomplishments, Dr. Lowenstein has received essentially every major award related to medical student education granted both locally at UCSF and nationally. He received multiple awards from the 1st and 2nd year classes at UCSF, including those for "A Major Contribution to Teaching," "Outstanding Lecture," "Outstanding Lecture Series," and "An Outstanding Role Model." Other major awards include the 1992 UCSF Academic Senate Distinction in Teaching Award, the 1993 and 1998 UCSF Kaiser Award for Excellence in Teaching, the UCSF Class of 1995 John V. Carbone Award for Excellence in Teaching, and Faculty Teaching Awards in 1994 and 1996. Dr. Lowenstein has given the Keynote Address for graduating medical students at Commencement Ceremonies at UCSF four times. In 1996, the UCSF students awarded him the American Medical Student Association (AMSA) Golden Apple Award for Excellence in Teaching. He went on to receive the AMSA 1997 National Golden Apple for Teaching Excellence Award, which is given to one medical school teacher in the country each year. In addition, the American Neurological Association (ANA) named him the first recipient of the ANA Distinguished Teacher Award in 1997, and in 1998 he was granted the Alpha Omega Alpha Robert J. Glaser Distinguished Teacher Award by the American Association of Medical Colleges.

In addition to his professional activities, Dr. Lowenstein is an avid skier and wilderness traveller who has hiked, climbed and canoed extensively throughout the world, including mountaineering and canoe expeditions in Asia, Central and South America, Canada and the United States.

Publications: 

Further delineation of the clinical spectrum of de novo TRIM8 truncating mutations.

American journal of medical genetics. Part A

Assoum M, Lines MA, Elpeleg O, Darmency V, Whiting S, Edvardson S, Devinsky O, Heinzen E, Hernan RR, Antignac C, Deleuze JF, Des Portes V, Bertholet-Thomas A, Belot A, Geller E, Lemesle M, Duffourd Y, Thauvin-Robinet C, Thevenon J, Chung W, Lowenstein DH, Faivre L

Return of individual results in epilepsy genomic research: A view from the field.

Epilepsia

Ottman R, Freyer C, Mefford HC, Poduri A, Lowenstein DH

The Psychiatric Cell Map Initiative: A Convergent Systems Biological Approach to Illuminating Key Molecular Pathways in Neuropsychiatric Disorders.

Cell

Willsey AJ, Morris MT, Wang S, Willsey HR, Sun N, Teerikorpi N, Baum TB, Cagney G, Bender KJ, Desai TA, Srivastava D, Davis GW, Doudna J, Chang E, Sohal V, Lowenstein DH, Li H, Agard D, Keiser MJ, Shoichet B, von Zastrow M, Mucke L, Finkbeiner S, Gan L, Sestan N, Ward ME, Huttenhain R, Nowakowski TJ, Bellen HJ, Frank LM, Khokha MK, Lifton RP, Kampmann M, Ideker T, State MW, Krogan NJ

Is seizure frequency variance a predictable quantity?

Annals of clinical and translational neurology

Goldenholz DM, Goldenholz SR, Moss R, French J, Lowenstein D, Kuzniecky R, Haut S, Cristofaro S, Detyniecki K, Hixson J, Karoly P, Cook M, Strashny A, Theodore WH

Commonalities in epileptogenic processes from different acute brain insults: Do they translate?

Epilepsia

Klein P, Dingledine R, Aronica E, Bernard C, Blümcke I, Boison D, Brodie MJ, Brooks-Kayal AR, Engel J, Forcelli PA, Hirsch LJ, Kaminski RM, Klitgaard H, Kobow K, Lowenstein DH, Pearl PL, Pitkänen A, Puhakka N, Rogawski MA, Schmidt D, Sillanpää M, Sloviter RS, Steinhäuser C, Vezzani A, Walker MC, Löscher W

A case-control collapsing analysis identifies epilepsy genes implicated in trio sequencing studies focused on de novo mutations.

PLoS genetics

Zhu X, Padmanabhan R, Copeland B, Bridgers J, Ren Z, Kamalakaran S, O'Driscoll-Collins A, Berkovic SF, Scheffer IE, Poduri A, Mei D, Guerrini R, Lowenstein DH, Allen AS, Heinzen EL, Goldstein DB

De Novo Mutations in PPP3CA Cause Severe Neurodevelopmental Disease with Seizures.

American journal of human genetics

Myers CT, Stong N, Mountier EI, Helbig KL, Freytag S, Sullivan JE, Ben Zeev B, Nissenkorn A, Tzadok M, Heimer G, Shinde DN, Rezazadeh A, Regan BM, Oliver KL, Ernst ME, Lippa NC, Mulhern MS, Ren Z, Poduri A, Andrade DM, Bird LM, Bahlo M, Berkovic SF, Lowenstein DH, Scheffer IE, Sadleir LG, Goldstein DB, Mefford HC, Heinzen EL

Does accounting for seizure frequency variability increase clinical trial power?

Epilepsy research

Goldenholz DM, Goldenholz SR, Moss R, French J, Lowenstein D, Kuzniecky R, Haut S, Cristofaro S, Detyniecki K, Hixson J, Karoly P, Cook M, Strashny A, Theodore WH, Pieper C

Heterozygous HNRNPU variants cause early onset epilepsy and severe intellectual disability.

Human genetics

Bramswig NC, Lüdecke HJ, Hamdan FF, Altmüller J, Beleggia F, Elcioglu NH, Freyer C, Gerkes EH, Demirkol YK, Knupp KG, Kuechler A, Li Y, Lowenstein DH, Michaud JL, Park K, Stegmann APA, Veenstra-Knol HE, Wieland T, Wollnik B, Engels H, Strom TM, Kleefstra T, Wieczorek D

Progress in Epilepsy: Latest Waves of Discovery.

JAMA neurology

Kleen JK, Lowenstein DH

Effect of waivers of consent on recruitment in acute stroke trials: A systematic review.

Neurology

Feldman WB, Kim AS, Josephson SA, Lowenstein DH, Chiong W

Number of patient-reported allergies helps distinguish epilepsy from psychogenic nonepileptic seizures.

Epilepsy & behavior : E&B

Robbins NM, Larimer P, Bourgeois JA, Lowenstein DH

Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults: Report of the Guideline Committee of the American Epilepsy Society.

Epilepsy currents

Glauser T, Shinnar S, Gloss D, Alldredge B, Arya R, Bainbridge J, Bare M, Bleck T, Dodson WE, Garrity L, Jagoda A, Lowenstein D, Pellock J, Riviello J, Sloan E, Treiman DM

A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus.

Epilepsia

Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, Shorvon S, Lowenstein DH

Epilepsy.

Current biology : CB

Rao VR, Lowenstein DH

Status epilepticus in adults.

The Lancet. Neurology

Betjemann JP, Lowenstein DH

SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients.

Neurobiology of disease

Haenisch S, Zhao Y, Chhibber A, Kaiboriboon K, Do LV, Vogelgesang S, Barbaro NM, Alldredge BK, Lowenstein DH, Cascorbi I, Kroetz DL

Intramuscular midazolam versus intravenous lorazepam for the prehospital treatment of status epilepticus in the pediatric population.

Epilepsia

Welch RD, Nicholas K, Durkalski-Mauldin VL, Lowenstein DH, Conwit R, Mahajan PV, Lewandowski C, Silbergleit R

De novo mutations in synaptic transmission genes including DNM1 cause epileptic encephalopathies

Am J Hum Genet

EuroEPINOMICS-RES Consortium; Epilepsy Phenome/Genome Project; Epi4K Consortium

Status epilepticus in the setting of acute encephalitis.

Epilepsy currents

Lowenstein DH, Walker M, Waterhouse E

The search for circulating epilepsy biomarkers.

Biomarkers in medicine

Hegde M, Lowenstein DH

Quo vadis? Peering into the future.

Annals of neurology

Hauser SL, Johnston SC, Ferriero DM, Josephson SA, Lowenstein DH, Messing RO, Oksenberg JR

Have the Annals editors added value?

Annals of neurology

Johnston SC, Ferriero DM, Josephson SA, Lowenstein DH, Messing RO, Oksenberg J, Stewart A, Hauser SL

Mental illness among us: a new curriculum to reduce mental illness stigma among medical students.

Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry

Aggarwal AK, Thompson M, Falik R, Shaw A, O'Sullivan P, Lowenstein DH

Lennox-Gastaut syndrome of unknown cause: phenotypic characteristics of patients in the Epilepsy Phenome/Genome Project.

Epilepsia

Widdess-Walsh P, Dlugos D, Fahlstrom R, Joshi S, Shellhaas R, Boro A, Sullivan J, Geller E

The established status epilepticus trial 2013.

Epilepsia

Bleck T, Cock H, Chamberlain J, Cloyd J, Connor J, Elm J, Fountain N, Jones E, Lowenstein D, Shinnar S, Silbergleit R, Treiman D, Trinka E, Kapur J

Acute seizures predict epilepsy after childhood stroke.

Annals of neurology

Fox CK, Glass HC, Sidney S, Lowenstein DH, Fullerton HJ

The epilepsy phenome/genome project.

Clinical trials (London, England)

Polymicrogyria-associated epilepsy: a multicenter phenotypic study from the Epilepsy Phenome/Genome Project.

Epilepsia

Shain C, Ramgopal S, Fallil Z, Parulkar I, Alongi R, Knowlton R, Poduri A

SCN1A testing for epilepsy: application in clinical practice.

Epilepsia

Hirose S, Scheffer IE, Marini C, De Jonghe P, Andermann E, Goldman AM, Kauffman M, Tan NC, Lowenstein DH, Sisodiya SM, Ottman R, Berkovic SF

Genetics of the epilepsies: where are we and where are we going?

Current opinion in neurology

Helbig I, Lowenstein DH

Epi4K: gene discovery in 4,000 genomes

Epilepsia

Epi4K Consortium

The Epilepsy Phenome/Genome Project (EPGP) informatics platform.

International journal of medical informatics

Nesbitt G, McKenna K, Mays V, Carpenter A, Miller K, Williams M

Implementation of the exception from informed consent regulations in a large multicenter emergency clinical trials network: the RAMPART experience.

Academic emergency medicine : official journal of the Society for Academic Emergency Medicine

Silbergleit R, Biros MH, Harney D, Dickert N, Baren J

Intramuscular versus intravenous therapy for prehospital status epilepticus.

The New England journal of medicine

Silbergleit R, Durkalski V, Lowenstein D, Conwit R, Pancioli A, Palesch Y, Barsan W

Fighting decision fatigue.

Annals of neurology

Stewart AF, Ferriero DM, Josephson SA, Lowenstein DH, Messing RO, Oksenberg JR, Johnston SC, Hauser SL

Neurological disorders in Iraqi refugees in Jordan: data from the United Nations Refugee Assistance Information System.

Journal of neurology

Mateen FJ, Carone M, Nyce S, Ghosn J, Mutuerandu T, Al-Saedy H, Lowenstein DH, Burnham G

Challenges in the design and analysis of non-inferiority trials: a case study.

Clinical trials (London, England)

Durkalski V, Silbergleit R, Lowenstein D

Common data elements in epilepsy research: development and implementation of the NINDS epilepsy CDE project.

Epilepsia

Loring DW, Lowenstein DH, Barbaro NM, Fureman BE, Odenkirchen J, Jacobs MP, Austin JK, Dlugos DJ, French JA, Gaillard WD, Hermann BP, Hesdorffer DC, Roper SN, Van Cott AC, Grinnon S, Stout A

Epilepsy genetics--past, present, and future.

Current opinion in genetics & development

Poduri A, Lowenstein D

Epilepsy and trauma: a persistent challenge.

Neurology

Willmore LJ, Lowenstein DH

Getting youth in the game: can we accelerate training for clinician-scientists?

Annals of neurology

Hauser SL, Lowenstein DH, Johnston SC

Status report: the Annals in 2010.

Annals of neurology

Hauser SL, Johnston SC, Ferriero DM, Lowenstein DH, Josephson SA, Messing RO, Oksenberg JR, Stewart AF

Harold Shaw and the Ross Sea Party: epilepsy in the Antarctic.

Journal of the history of the neurosciences

Devinsky J, Lowenstein D, McElrea R

Curing epilepsy: progress and future directions.

Epilepsy & behavior : E&B

Jacobs MP, Leblanc GG, Brooks-Kayal A, Jensen FE, Lowenstein DH, Noebels JL, Spencer DD, Swann JW

The NINDS epilepsy research benchmarks.

Epilepsia

Kelley MS, Jacobs MP, Lowenstein DH

Invited article: Neurology education research.

Neurology

Stern BJ, Lowenstein DH, Schuh LA

Refractory status epilepticus in suspect encephalitis.

Neurocritical care

Glaser CA, Gilliam S, Honarmand S, Tureen JH, Lowenstein DH, Anderson LJ, Bollen AW, Solbrig MV

Epilepsy genetics: yet more exciting news.

Annals of neurology

Lowenstein D, Messing R

Pharmacoresistant epilepsy: if at first you don't succeed...

Annals of neurology

Shih T, Lowenstein D

Early editorial manuscript screening versus obligate peer review: a randomized trial.

Annals of neurology

Johnston SC, Lowenstein DH, Ferriero DM, Messing RO, Oksenberg JR, Hauser SL

Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy.

Annals of neurology

Parent JM, Elliott RC, Pleasure SJ, Barbaro NM, Lowenstein DH

Treatment options for status epilepticus.

Current opinion in pharmacology

Lowenstein DH

Laminar organization of the mouse dentate gyrus: insights from BETA2/Neuro D mutant mice.

The Journal of comparative neurology

Del Turco D, Gebhardt C, Burbach GJ, Pleasure SJ, Lowenstein DH, Deller T

The academy movement: a structural approach to reinvigorating the educational mission.

Academic medicine : journal of the Association of American Medical Colleges

Irby DM, Cooke M, Lowenstein D, Richards B

Gene expression profiling of seizure disorders.

Neurochemical research

Elliott RC, Lowenstein DH

Epilepsy.

The New England journal of medicine

Chang BS, Lowenstein DH

The Academy at Harvard Medical School: nurturing teaching and stimulating innovation.

Academic medicine : journal of the Association of American Medical Colleges

Thibault GE, Neill JM, Lowenstein DH

Overlapping microarray profiles of dentate gyrus gene expression during development- and epilepsy-associated neurogenesis and axon outgrowth.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Elliott RC, Miles MF, Lowenstein DH

Treatment options for status epilepticus.

Current opinion in pharmacology

Lowenstein DH

Models for epilepsy and epileptogenesis: report from the NIH workshop, Bethesda, Maryland.

Epilepsia

Stables JP, Bertram EH, White HS, Coulter DA, Dichter MA, Jacobs MP, Loscher W, Lowenstein DH, Moshe SL, Noebels JL, Davis M

The Academies Collaborative: sharing a new model for medical education.

Academic medicine : journal of the Association of American Medical Colleges

Rider EA, Cooke M, Lowenstein D

Prolonged seizures increase proliferating neuroblasts in the adult rat subventricular zone-olfactory bulb pathway.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Parent JM, Valentin VV, Lowenstein DH

Seizure-induced neurogenesis: are more new neurons good for an adult brain?

Progress in brain research

Parent JM, Lowenstein DH