Louis Ptacek, MD

Professor in Residence
Neurology
+1 415 514-9305

Episodic phenomena (epilepsy, migraine, and cardiac arrhythmias) are among the most common disorders afflicting humans. Early in his career, Ptácek began studying patients with rare Mendelian muscle disorders (periodic paralysis) and proposed these as a model of more common episodic disorders. In 1990, he began systematically characterizing genes causing familial forms of periodic paralysis. This series of landmark discoveries identified mutant ion channel genes and laid the groundwork for the field now called the "channelopathies." He proposed that all the work in channelopathies of skeletal muscle would be model for episodic disorders of heart and brain. Subsequently, his group and others have identified homologous genes that (when mutated) cause cardiac arrhythmias, epilepsy, and migraine. He has gone from describing new syndromes to cloning causative genes, to biological study in vitro and in vivo (animal models).

More recently, Ptácek led the team that characterized the first Mendelian variant in human circadian function. He and his colleague Ying-Hui Fu have gone on to clone and characterize numerous genes causing this phenotype. This work has led to novel insights into human circadian biology.

Ptácek is an HHMI Investigator, and an associate editor of The Journal of Clinical Investigation and Neurogenetics. He is a member of the American Academy of Arts and Sciences, the Institute of Medicine, and the National Academy of Science.

Publications: 

Proceedings of the Sleep and Epilepsy Workshop: Section 1 Decreasing Seizures-Improving Sleep and Seizures, Themes for Future Research.

Epilepsy currents

Quigg M, Bazil CW, Boly M, St Louis EK, Liu J, Ptacek L, Maganti R, Kalume F, Gluckman BJ, Pathmanathan J, Pavlova MK, Buchanan GF

Developing the field of neurogenetics.

Neurogenetics

Müller U, Auburger G, Graeber MB, Ptacek LJ

Sleep and Mood: Chicken or Egg?

Biological psychiatry

Ptáoek LJ, Fu YH, Krystal AD

Impact of Sleep and Circadian Disruption on Energy Balance and Diabetes: A Summary of Workshop Discussions.

Sleep

Arble DM, Bass J, Behn CD, Butler MP, Challet E, Czeisler C, Depner CM, Elmquist J, Franken P, Grandner MA, Hanlon EC, Keene AC, Joyner MJ, Karatsoreos I, Kern PA, Klein S, Morris CJ, Pack AI, Panda S, Ptacek LJ, Punjabi NM, Sassone-Corsi P, Scheer FA, Saxena R, Seaquest ER, Thimgan MS, Van Cauter E, Wright KP

Protein mutated in paroxysmal dyskinesia interacts with the active zone protein RIM and suppresses synaptic vesicle exocytosis.

Proceedings of the National Academy of Sciences of the United States of America

Shen Y, Ge WP, Li Y, Hirano A, Lee HY, Rohlmann A, Missler M, Tsien RW, Jan LY, Fu YH, Ptácek LJ

Episodic disorders: channelopathies and beyond.

Annual review of physiology

Ptácek LJ

Genetics of human sleep behavioral phenotypes.

Methods in enzymology

Hsu PK, Ptácek LJ, Fu YH

Andersen-Tawil syndrome: report of 3 novel mutations and high risk of symptomatic cardiac involvement.

Muscle & nerve

Kostera-Pruszczyk A, Potulska-Chromik A, Pruszczyk P, Bieganowska K, Miszczak-Knecht M, Bienias P, Szczaluba K, Lee HY, Quinn E, Ploski R, Kaminska A, Ptácek LJ

Episodic and electrical nervous system disorders caused by nonchannel genes.

Annual review of physiology

Lee HY, Fu YH, Ptácek LJ

Regulation of Myelination in the Central Nervous System by Nuclear Lamin B1 and Non-coding RNAs.

Translational neurodegeneration

Lin ST, Heng MY, Ptácek LJ, Fu YH

Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gαs/Gαq-mediated protein kinases A/C.

Proceedings of the National Academy of Sciences of the United States of America

Shin D, Lin ST, Fu YH, Ptácek LJ

MicroRNA-23a promotes myelination in the central nervous system.

Proceedings of the National Academy of Sciences of the United States of America

Lin ST, Huang Y, Zhang L, Heng MY, Ptácek LJ, Fu YH

Solving the mystery of human sleep schedules one mutation at a time.

Critical reviews in biochemistry and molecular biology

Hallows WC, Ptácek LJ, Fu YH

Sick and tired: how molecular regulators of human sleep schedules and duration impact immune function.

Current opinion in neurobiology

Kurien PA, Chong SY, Ptácek LJ, Fu YH

Lamin B1 mediates cell-autonomous neuropathology in a leukodystrophy mouse model.

The Journal of clinical investigation

Heng MY, Lin ST, Verret L, Huang Y, Kamiya S, Padiath QS, Tong Y, Palop JJ, Huang EJ, Ptácek LJ, Fu YH

Casein kinase iδ mutations in familial migraine and advanced sleep phase.

Science translational medicine

Brennan KC, Bates EA, Shapiro RE, Zyuzin J, Hallows WC, Huang Y, Lee HY, Jones CR, Fu YH, Charles AC, Ptácek LJ

Episodic neurologic disorders: syndromes, genes, and mechanisms.

Annual review of neuroscience

Russell JF, Fu YH, Ptácek LJ

Dual roles of FBXL3 in the mammalian circadian feedback loops are important for period determination and robustness of the clock.

Proceedings of the National Academy of Sciences of the United States of America

Shi G, Xing L, Liu Z, Qu Z, Wu X, Dong Z, Wang X, Gao X, Huang M, Yan J, Yang L, Liu Y, Ptácek LJ, Xu Y

Glucose sensor O-GlcNAcylation coordinates with phosphorylation to regulate circadian clock.

Cell metabolism

Kaasik K, Kivimäe S, Allen JJ, Chalkley RJ, Huang Y, Baer K, Kissel H, Burlingame AL, Shokat KM, Ptácek LJ, Fu YH

Diversity of human clock genotypes and consequences.

Progress in molecular biology and translational science

Zhang L, Ptácek LJ, Fu YH

PKCγ participates in food entrainment by regulating BMAL1.

Proceedings of the National Academy of Sciences of the United States of America

Zhang L, Abraham D, Lin ST, Oster H, Eichele G, Fu YH, Ptácek LJ

PRRT2 links infantile convulsions and paroxysmal dyskinesia with migraine.

Neurology

Cloarec R, Bruneau N, Rudolf G, Massacrier A, Salmi M, Bataillard M, Boulay C, Caraballo R, Fejerman N, Genton P, Hirsch E, Hunter A, Lesca G, Motte J, Roubertie A, Sanlaville D, Wong SW, Fu YH, Rochette J, Ptácek LJ, Szepetowski P

An inwardly rectifying K+ channel is required for patterning.

Development (Cambridge, England)

Dahal GR, Rawson J, Gassaway B, Kwok B, Tong Y, Ptácek LJ, Bates E

Genetic insights on sleep schedules: this time, it's PERsonal.

Trends in genetics : TIG

Chong SY, Ptácek LJ, Fu YH

Familial cortical myoclonus with a mutation in NOL3.

Annals of neurology

Russell JF, Steckley JL, Coppola G, Hahn AF, Howard MA, Kornberg Z, Huang A, Mirsattari SM, Merriman B, Klein E, Choi M, Lee HY, Kirk A, Nelson-Williams C, Gibson G, Baraban SC, Lifton RP, Geschwind DH, Fu YH, Ptácek LJ

Genetic basis of human circadian rhythm disorders.

Experimental neurology

Jones CR, Huang AL, Ptácek LJ, Fu YH

Casein kinase 1 proteomics reveal prohibitin 2 function in molecular clock.

PloS one

Kategaya LS, Hilliard A, Zhang L, Asara JM, Ptácek LJ, Fu YH

Dopamine dysregulation in a mouse model of paroxysmal nonkinesigenic dyskinesia.

The Journal of clinical investigation

Lee HY, Nakayama J, Xu Y, Fan X, Karouani M, Shen Y, Pothos EN, Hess EJ, Fu YH, Edwards RH, Ptácek LJ

Mutations in the gene PRRT2 cause paroxysmal kinesigenic dyskinesia with infantile convulsions.

Cell reports

Lee HY, Huang Y, Bruneau N, Roll P, Roberson ED, Hermann M, Quinn E, Maas J, Edwards R, Ashizawa T, Baykan B, Bhatia K, Bressman S, Bruno MK, Brunt ER, Caraballo R, Echenne B, Fejerman N, Frucht S, Gurnett CA, Hirsch E, Houlden H, Jankovic J, Lee WL, Lynch DR, Mohammed S, Müller U, Nespeca MP, Renner D, Rochette J, Rudolf G, Saiki S, Soong BW, Swoboda KJ, Tucker S, Wood N, Hanna M, Bowcock AM, Szepetowski P, Fu YH, Ptácek LJ

Circadian rhythm gene period 3 is an inhibitor of the adipocyte cell fate.

The Journal of biological chemistry

Costa MJ, So AY, Kaasik K, Krueger KC, Pillsbury ML, Fu YH, Ptacek LJ, Yamamoto KR, Feldman BJ

The genetics of the human circadian clock.

Advances in genetics

Zhang L, Jones CR, Ptacek LJ, Fu YH

Novel familial cases of ICCA (infantile convulsions with paroxysmal choreoathetosis) syndrome.

Epileptic disorders : international epilepsy journal with videotape

Rochette J, Roll P, Fu YH, Lemoing AG, Royer B, Roubertie A, Berquin P, Motte J, Wong SW, Hunter A, Robaglia-Schlupp A, Ptacek LJ, Szepetowski P

In memoriam: Louis John Ptácek, Sr, MD (1929-2006).

Journal of child neurology

Ptácek LJ

Paroxysmal non-kinesigenic dyskinesia caused by the mutation of MR-1 in a large Polish kindred.

European neurology

Friedman A, Zakrzewska-Pniewska B, Domitrz I, Lee HY, Ptacek L, Kwiecinski H

Proteolytic cleavage of ataxin-7 by caspase-7 modulates cellular toxicity and transcriptional dysregulation.

The Journal of biological chemistry

Young JE, Gouw L, Propp S, Sopher BL, Taylor J, Lin A, Hermel E, Logvinova A, Chen SF, Chen S, Bredesen DE, Truant R, Ptacek LJ, La Spada AR, Ellerby LM

FAME 3: a novel form of progressive myoclonus and epilepsy.

Neurology

Carr JA, van der Walt PE, Nakayama J, Fu YH, Corfield V, Brink P, Ptacek L

Deletions in CCM2 are a common cause of cerebral cavernous malformations.

American journal of human genetics

Liquori CL, Berg MJ, Squitieri F, Leedom TP, Ptacek L, Johnson EW, Marchuk DA

Array comparative genomic hybridization in patients with congenital diaphragmatic hernia: mapping of four CDH-critical regions and sequencing of candidate genes at 15q26.1-15q26.2.

European journal of human genetics : EJHG

Slavotinek AM, Moshrefi A, Davis R, Leeth E, Schaeffer GB, Burchard GE, Shaw GM, James B, Ptacek L, Pennacchio LA

Low frequency of PDCD10 mutations in a panel of CCM3 probands: potential for a fourth CCM locus.

Human mutation

Liquori CL, Berg MJ, Squitieri F, Ottenbacher M, Sorlie M, Leedom TP, Cannella M, Maglione V, Ptacek L, Johnson EW, Marchuk DA

Clinical feature profile of spinocerebellar ataxia type 1-8 predicts genetically defined subtypes.

Movement disorders : official journal of the Movement Disorder Society

Maschke M, Oehlert G, Xie TD, Perlman S, Subramony SH, Kumar N, Ptacek LJ, Gomez CM

The primary periodic paralyses: diagnosis, pathogenesis and treatment.

Brain : a journal of neurology

Venance SL, Cannon SC, Fialho D, Fontaine B, Hanna MG, Ptacek LJ, Tristani-Firouzi M, Tawil R, Griggs RC, CINCH investigators

Electrocardiographic features in Andersen-Tawil syndrome patients with KCNJ2 mutations: characteristic T-U-wave patterns predict the KCNJ2 genotype.

Circulation

Zhang L, Benson DW, Tristani-Firouzi M, Ptacek LJ, Tawil R, Schwartz PJ, George AL, Horie M, Andelfinger G, Snow GL, Fu YH, Ackerman MJ, Vincent GM

Auditory deficits associated with the frings mgr1 (mass1) mutation in mice.

Developmental neuroscience

Klein BD, Fu YH, Ptacek LJ, White HS

Clinical evaluation of idiopathic paroxysmal kinesigenic dyskinesia: new diagnostic criteria.

Neurology

Bruno MK, Hallett M, Gwinn-Hardy K, Sorensen B, Considine E, Tucker S, Lynch DR, Mathews KD, Swoboda KJ, Harris J, Soong BW, Ashizawa T, Jankovic J, Renner D, Fu YH, Ptacek LJ

Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel ATP1A2 mutation.

Annals of neurology

Swoboda KJ, Kanavakis E, Xaidara A, Johnson JE, Leppert MF, Schlesinger-Massart MB, Ptacek LJ, Silver K, Youroukos S

Exercise-induced dystonia as a preceding symptom of familial Parkinson's disease.

Movement disorders : official journal of the Movement Disorder Society

Bruno MK, Ravina B, Garraux G, Hallett M, Ptacek L, Singleton A, Johnson J, Singleton A, Hanson M, Considine E, Gwinn-Hardy K

Mutations in a gene encoding a novel protein containing a phosphotyrosine-binding domain cause type 2 cerebral cavernous malformations.

American journal of human genetics

Liquori CL, Berg MJ, Siegel AM, Huang E, Zawistowski JS, Stoffer T, Verlaan D, Balogun F, Hughes L, Leedom TP, Plummer NW, Cannella M, Maglione V, Squitieri F, Johnson EW, Rouleau GA, Ptacek L, Marchuk DA

A novel central nervous system-enriched spinocerebellar ataxia type 7 gene product.

Archives of neurology

Einum DD, Clark AM, Townsend JJ, Ptacek LJ, Fu YH

Genomic context drives SCA7 CAG repeat instability, while expressed SCA7 cDNAs are intergenerationally and somatically stable in transgenic mice.

Human molecular genetics

Libby RT, Monckton DG, Fu YH, Martinez RA, McAbney JP, Lau R, Einum DD, Nichol K, Ware CB, Ptacek LJ, Pearson CE, La Spada AR

Functional and clinical characterization of KCNJ2 mutations associated with LQT7 (Andersen syndrome).

The Journal of clinical investigation

Tristani-Firouzi M, Jensen JL, Donaldson MR, Sansone V, Meola G, Hahn A, Bendahhou S, Kwiecinski H, Fidzianska A, Plaster N, Fu YH, Ptacek LJ, Tawil R

Polyglutamine-expanded ataxin-7 promotes non-cell-autonomous purkinje cell degeneration and displays proteolytic cleavage in ataxic transgenic mice.

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

Garden GA, Libby RT, Fu YH, Kinoshita Y, Huang J, Possin DE, Smith AC, Martinez RA, Fine GC, Grote SK, Ware CB, Einum DD, Morrison RS, Ptacek LJ, Sopher BL, La Spada AR

Channelopathies: episodic disorders of the nervous system.

Novartis Foundation symposium

Ptacek L

MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis.

Cell

Abbott GW, Butler MH, Bendahhou S, Dalakas MC, Ptacek LJ, Goldstein SA

Randomized trials of dichlorphenamide in the periodic paralyses. Working Group on Periodic Paralysis.

Annals of neurology

Tawil R, McDermott MP, Brown R, Shapiro BC, Ptacek LJ, McManis PG, Dalakas MC, Spector SA, Mendell JR, Hahn AF, Griggs RC

Anesthetic management of familial hypokalemic periodic paralysis during parturition.

Anesthesia and analgesia

Viscomi CM, Ptacek LJ, Dudley D

Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27.

Human molecular genetics

Craig HD, Günel M, Cepeda O, Johnson EW, Ptacek L, Steinberg GK, Ogilvy CS, Berg MJ, Crawford SC, Scott RM, Steichen-Gersdorf E, Sabroe R, Kennedy CT, Mettler G, Beis MJ, Fryer A, Awad IA, Lifton RP

Autosomal dominant cerebral arteriopathy: neuropsychiatric syndrome in a family.

Neuropsychiatry, neuropsychology, and behavioral neurology

Adair JC, Hart BL, Kornfeld M, Graham GD, Swanda RM, Ptacek LJ, Davis LE

A new locus for hemiplegic migraine maps to chromosome 1q31.

Neurology

Gardner K, Barmada MM, Ptacek LJ, Hoffman EP

An expanded CAG repeat sequence in spinocerebellar ataxia type 7.

Genome research

Lindblad K, Savontaus ML, Stevanin G, Holmberg M, Digre K, Zander C, Ehrsson H, David G, Benomar A, Nikoskelainen E, Trottier Y, Holmgren G, Ptacek LJ, Anttinen A, Brice A, Schalling M

Mutation in the S4 segment of the adult skeletal sodium channel gene in an Italian paramyotonia congenita (PC) family.

Italian journal of neurological sciences

Sansone V, Rotondo G, Ptacek LJ, Meola G

Andersen's syndrome: potassium-sensitive periodic paralysis, ventricular ectopy, and dysmorphic features.

Annals of neurology

Tawil R, Ptacek LJ, Pavlakis SG, DeVivo DC, Penn AS, Ozdemir C, Griggs RC

Sodium channel mutations in paramyotonia congenita and hyperkalemic periodic paralysis.

Annals of neurology

Ptacek LJ, Gouw L, Kwiecinski H, McManis P, Mendell JR, Barohn RJ, George AL, Barchi RL, Robertson M, Leppert MF

Genetics and physiology of the myotonic muscle disorders.

The New England journal of medicine

Ptacek LJ, Johnson KJ, Griggs RC

Evidence of genetic heterogeneity among the nondystrophic myotonias.

Neurology

Ptacek LJ, Ziter FA, Roberts JW, Leppert MF

Linkage of atypical myotonia congenita to a sodium channel locus.

Neurology

Ptacek LJ, Tawil R, Griggs RC, Storvick D, Leppert M

Paramyotonia congenita and hyperkalemic periodic paralysis map to the same sodium-channel gene locus.

American journal of human genetics

Ptacek LJ, Trimmer JS, Agnew WS, Roberts JW, Petajan JH, Leppert M

Analysis in a large hyperkalemic periodic paralysis pedigree supports tight linkage to a sodium channel locus.

American journal of human genetics

Ptacek LJ, Tyler F, Trimmer JS, Agnew WS, Leppert M

Fetal anticonvulsant drug exposure: a population based study.

Neurotoxicology

Robertson LD, Swaiman KF, Ptacek LJ

STROBOSCOPIC-INDUCED SEIZURE DISCHARGES. MODIFICATION BY EXTINCTION TECHNIQUES.

Archives of neurology

FORSTER FM, PTACEK LJ, PETERSON WG, CHUN RW, BENGZON AR, CAMPOS GB

Research Area: 
Central Regulation
Human Genetics