Update Your ProfileAcademic Title:
Professor
Primary Appointment:
Neurology
Secondary Appointment(s):
Neurobiology, Psychiatry
Administrative Title:
Chair, Department of Neurology
Location:
UMMC
Phone (Primary):
410-328-6266
Fax:
410-328-0697
Education and Training
- Binghamton University, BA, Psychology/Philosophy
- Yale University Medical School, MD
- Yale New Haven Hospital, Internship, Internal Medicine
- Boston University, PhD, Neuroscience
- University of Pennsylvania, Howard Hughes Medical Institute Physician Post-Doctoral Fellow; Clinical Epilepsy Fellow
- University of Pennsylvania, Residency, Neurology
Biosketch
Dr. Crino is an internationally recognized physician-scientist specializing in developmental brain disorders. His laboratory has researched mechanisms of altered brain development associated with autism, intellectual disability, and epilepsy, defining developmental disorders associated with intractable epilepsy including autism, hemimegalencephaly, focal cortical dysplasia, and tuberous sclerosis complex (TSC), which he has studied extensively. He has collaborated on identifying several new genes associated with neurodevelopmental disorders, pioneered single cell mRNA and DNA sequencing analysis in resected human tissues; and has used mouse models to plumb the effects of mTOR regulatory genes on cell development in in vitro models using immunocytochemistry, Western assay, mRNA expression analysis, gene transfection, and in vitro cell migration assays.
Before his appointment to Chairman of the UMSOM Department of Neurology, Dr. Crino was professor and vice chair for research at Temple University School of Medicine’s Shriners Hospital Pediatric Research Center in Philadelphia. Over the last 20 years, his lab has had continuous funding from the National Institutes of Health, through which he has four grants totaling $4.1 million. He has coauthored 151 peer-reviewed manuscripts, chapters, and reviews. He has been invited to lecture all over the world.
Research/Clinical Keywords
Epilepsy, Autism, Intellectual Disability, Brain Development, Translational Neuroscience, mTOR, focal cortical dysplasia, tuberous sclerosis complex
Highlighted Publications
The mTOR signalling cascade: paving new roads to cure neurological disease. Crino PB. Nat Rev Neurol. 2016 12(7):379-92.
Novel Histopathological Patterns in Cortical Tubers of Epilepsy Surgery Patients with Tuberous Sclerosis Complex. Mühlebner A, van Scheppingen J, Hulshof HM, Scholl T, Iyer AM, Anink JJ, van den Ouweland AM, Nellist MD, Jansen FE, Spliet WG, Krsek P, Benova B, Zamecnik J, Crino PB, Prayer D, Czech T, Wöhrer A, Rahimi J, Höftberger R, Hainfellner JA, Feucht M, Aronica E. PLoS One. 2016 11(6):e0157396.
Mutations in TBCK, Encoding TBC1-Domain-Containing Kinase, Lead to a Recognizable Syndrome of Intellectual Disability and Hypotonia. Bhoj EJ, Li D, Harr M, Edvardson S, Elpeleg O, Chisholm E, Juusola J, Douglas G, Guillen Sacoto MJ, Siquier-Pernet K, Saadi A, Bole-Feysot C, Nitschke P, Narravula A, Walke M, Horner MB, Day-Salvatore DL, Jayakar P, Vergano SA, Tarnopolsky MA, Hegde M, Colleaux L, Crino P, Hakonarson H. Am J Hum Genet. 2016 98(4):782-8.
mTOR pathway inhibition prevents neuroinflammation and neuronal death in a mouse model of cerebral palsy. Srivastava IN, Shperdheja J, Baybis M, Ferguson T, Crino PB. Neurobiol Dis. 2016;85:144-54.
Impaired Reelin-Dab1 Signaling Contributes to Neuronal Migration Deficits of Tuberous Sclerosis Complex. Moon UY, Park JY, Park R, Cho JY, Hughes LJ, McKenna J 3rd, Goetzl L, Cho SH, Crino PB, Gambello MJ, Kim S. Cell Rep. 2015 2(6):965-78.
Rapamycin prevents seizures after depletion of STRADA in a rare neurodevelopmental disorder. Parker WE, Orlova KA, Parker WH, Birnbaum JF, Krymskaya VP, Goncharov DA, Baybis M, Helfferich J, Okochi K, Strauss KA, Crino PB. Sci Transl Med. 2013; 5(182):182ra53.
Research Interests
My lab has maintained an NIH funded translational research program studying developmental brain malformations linked to epilepsy, autism, and intellectual disabilities for the past 20 years. We have specific expertise in defining developmental disorders associated with aberrant mTOR signaling and we were the first lab to define altered mTOR signaling to define the family of mTOR associated disorders (“mTORopathies”; see Crino, 2011) including focal cortical dysplasia (FCD), hemimegalencephaly, ganglioglioma, and Pretzel syndrome (PS). A major focus of my lab over the past 2 decades has been tuberous sclerosis complex (TSC) in which we have worked on human brain tissue biomarkers as well as mouse and in vitro models.
My lab has successfully implemented numerous experimental strategies in resected human tissues including immunohistochemistry, stereology, Western analysis, mRNA expression analysis, and DNA mutation analysis. We have successfully implemented cell culture model systems to study the effects of mTOR genes such as Tsc1Tsc2, and STRADA, in in vitro models on cell development using immunocytochemistry, Western assay, mRNA expression analysis, gene transfection, and in vitro cell migration assays.
In addition, we have optimized and implemented strategies in fetal mouse cortex using in utero electroporation to study the cell lineage marker, cell size, and cell signaling assays. We have extensive experience testing pharmacological compounds such as the mTOR pathway inhibitors in cell culture and live animals. My recent collaborations have helped to describe mutations in GATOR1 complex proteins (NPRL3 and DEPDC5) in FCD (Scerri et al., 2015; Sim et al., 2015).
Clinical Specialty Details
As a clinician-scientist, I have maintained a translational work approach over the past 20 years by serving as a clinical neurologist and epileptologist (double-boarded in Neurology and Clinical Neurophysiology) and have cared for literally thousands of epilepsy patients. I established the first adult TSC clinic in the US at UPENN in 1998 and then, formed a new TSC clinic at Temple University in 2012.
I served as Director of the UPENN Epilepsy Center from 2007-2012, a large tertiary care referral center and supervised several hundred epilepsy surgeries, many in patients with MCD. I have served on several advisory boards related to TSC, cortical malformations, and epilepsy. I have served on two independent international task forces to establish diagnostic criteria for TSC and FCD. I see adult patients from age 12 and up with intellectual disability and epilepsy.
Awards and Affiliations
- Member, American Academy of Neurology
- Member, American Epilepsy Society
- Member, American Clinical Neurophysiology Society
- Member, Board of Directors of the Tuberous Sclerosis Alliance
- Lifetime Service Award, Tuberous Sclerosis Alliance, 2008
- Member, Developmental Brain Disorders Study Section at NINDS
- Program Chair, the American Epilepsy Society 2016 Meeting
- Chair, 2105 Society of Neuroscience Neurobiology of Disease Workshop
- President, Philadelphia Neurological Society, 2016
Grants and Contracts
NINDS R41NS093970-01 (9/30/2015-8/31/2016)
“mTOR Substrate Phosphorylation: A New Bioassay for Therapeutics”
Principal Investigator, Crino
This grant is an STTR application to support collaborative academic and commercial work with Cognizance Biomarkers LLC to discover how mTOR inhibitors alter mTOR signaling as a bioassay in clinical settings.
NINDS R01NS089552-01 EUREKA (9/30/2014 – 07/31/2018)
“Discovery of Novel Molecular Abnormalities Underlying Non-Lesional Focal Epilepsy”
Co-Principal Investigator, Crino
The purpose of this grant is to investigate somatic gene mutations in non-lesional neocortical epilepsy and to functionally characterize new mutations in vitro.
NINDS R01NS082343-01 (10/1/13-4/1/17)
“Detection of Human Papilloma Virus in Cortical Dysplasia”
Principal Investigator, Crino
The purpose of this grant is to define the role of human papilloma and other viruses in developmental brain malformations associated with intellectual disability and epilepsy.
Professional Activity
- National Alliance for Autism Research (NAAR): Tissue Advisory Board 1997-2003
- Parents Against Childhood Epilepsy (PACE): Medical Advisory Board 1997-present
- Tuberous Sclerosis Alliance (TSA): Chairman, Professional Advisory Board 2001-2004
- Tuberous Sclerosis Alliance (TSA): Member, Board of Directors 2007-present
- Merritt-Putnam Symposium Advisory Board 2001-2002
- National Disease Research Interchange (NDRI): Member, Board of Directors, 2004-2007
- Contributing Editor: Epilepsy Currents 1997-2003
- ILAE Task Force on Cortical Dysplasia 2009-2010
- AES Investigator’s Workshop Committee 2010-2013
- AES Scientific Program Committee 2008-2011
- AES Anti-Epileptic Therapy (AET) Symposium Committee 2012-2015
- ZHD1 MCHG-B S.E.P. Study Section, 2001
- ZNS1 SRB-H Study Section, 2002
- ZRG-1 SSS-5 Study Section, 2003
- Member NCI "Mechanisms of Cell Signaling in Cancer" Special Emphasis Panel (SEP), September 2011
- Chair, Department of Defense (DOD) - Tuberous Sclerosis Complex CDMRP Review Panel, July 2012
- NINDS Molecular Neurogenetics (MNG) Study Section, September 2014
- Member, NINDS Developmental Brain Disorders (DBD) Study Section 2015-2021
- Co-Chair, Neurobiology of Disease Workshop, Society for Neuroscience, 2015
- Program Chair, American Epilepsy Society meeting 2015-2016
- President, Philadelphia Neurological Society, 2015-2016
Links of Interest
Previous Positions
- Faculty in the Department of Neurology, University of Pennsylvania, Philadelphia. Promoted to associate professor with tenure in 2004. Served as Director of the PENN Epilepsy Program, 2006-2012
- Faculty, Temple University School of Medicine, Philadelphia, 2012. Served as Professor, Vice Chair for Research and Director, Temple University Comprehensive Epilepsy Center