Marta Margeta, MD, PhD

Associate Professor
Pathology
+1 415 514-0228

Abnormal excitability contributes to neurologic disease pathogenesis either by impairing cell function or by increasing cellular susceptibility to injury. In most neurologic diseases, the pathologic process does not involve the entire neuromuscular unit. Instead, only specific subsets of neurons, glial cells, or muscle fibers are injured or die, and the nature of this selective injury determines the symptoms and clinical course of each disease. The long-term goal of our laboratory is to elucidate how ion channel signaling and metabolic abnormalities contribute to the selective vulnerability of different cell populations and thus influence onset and/or progression of different neurologic disorders. To accomplish this goal, we use cell culture and mouse models and a combination of different approaches (molecular and cell biology, immunohistochemistry, in situhybridization, imaging, biochemistry, and electrophysiology) to investigate two distinct but related areas:

(1) The function of intrinsic antioxidant signaling in the brain and skeletal muscle. Our aim is to define the role of endogenous antioxidant pathways in cellular susceptibility to injury, to elucidate how these pathways are regulated by neuronal activity, and to determine how these pathways modulate ion channel signaling in neurons, glia, and skeletal muscle fibers. Our current focus is on the Keap1/Nrf2/ARE pathway, which regulates the coordinated expression of a battery of antioxidant and phase II detoxification enzymes in response to a mild oxidative or ER stress in many different tissues, including the brain and skeletal muscle.

(2) Autophagy impairment and neurologic disease. In animal models, autophagy deficiency results in neurodegeneration and skeletal muscle atrophy; little, however, is known about the role of autophagy in normal neurologic function. We seek to elucidate why the consequences of autophagy deficiency (failure of autophagy initiation) and autophagy impairment (block of autophagy completion) differ in the skeletal muscle but are the same in the brain, to determine how autophagy regulates intrinsic antioxidant pathways and cellular excitability, and to establish how autophagy failure contributes to neuromuscular disease pathogenesis.

Our laboratory is also pursuing translational research with a goal to improve tissue-based diagnostics of neuromuscular diseases. To learn more about ongoing basic and translational research projects, please visit our lab Website.

Interests: Keap1/Nrf2 stress response pathway, redox signaling, autophagy, vacuolar myopathies, dermatomyositis, polymyositis, inclusion body myositis, colchicine, chloroquine

Publications: 

Effects of gene replacement therapy with resamirigene bilparvovec (AT132) on skeletal muscle pathology in X-linked myotubular myopathy: results from a substudy of the ASPIRO open-label clinical trial.

EBioMedicine

Lawlor MW, Schoser B, Margeta M, Sewry CA, Jones KA, Shieh PB, Kuntz NL, Smith BK, Dowling JJ, Müller-Felber W, Bönnemann CG, Seferian AM, Blaschek A, Neuhaus S, Foley AR, Saade DN, Tsuchiya E, Qasim UR, Beatka M, Prom MJ, Ott E, Danielson S, Krakau P, Kumar SN, Meng H, Vanden Avond M, Wells C, Gordish-Dressman H, Beggs AH, Christensen S, Conner E, James ES, Lee J, Sadhu C, Miller W, Sepulveda B, Varfaj F, Prasad S, Rico S

Neuromuscular disease: 2023 update.

Free neuropathology

Margeta M

Where is the field of autophagy research heading?

Autophagy

Abeliovich H, Debnath J, Ding WX, Jackson WT, Kim DH, Klionsky DJ, Ktistakis N, Margeta M, Münz C, Petersen M, Sadoshima J, Vergne I

Essential laboratory tests for medical education.

Academic pathology

Deyrup AT, D'Ambrosio D, Muir J, Laboratory Test Working Group, Knollmann-Ritschel B

Neuromuscular Disease: 2022 Update

Free Neuropathol

Margeta, M.

Neuromuscular disease: 2022 update.

Free neuropathology

Margeta M

COVID-19-associated Critical Illness Myopathy with Direct Viral Effects.

Annals of neurology

Dodig D, Tarnopolsky MA, Margeta M, Gordon K, Fritzler MJ, Lu JQ

Presenter: Werner Paulus, University Hospital Muenster, Muenster. Publishing A High-quality, Non-commercial Neuropathology Journal Without a Publisher: The First Nine Months.

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques

Marta Margeta, Peter Gould, Lili-Naz Hazrati, Veronica Hirsch-Reinshagen, Werner Paulus

Neuromuscular Disease: 2021 Update

Free Neuropathol

Margeta, M.

Neuromuscular disease: 2021 update.

Free neuropathology

Margeta M

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

Autophagy

Klionsky DJ, Abdel-Aziz AK, Abdelfatah S, Abdellatif M, Abdoli A, Abel S, Abeliovich H, Abildgaard MH, Abudu YP, Acevedo-Arozena A, Adamopoulos IE, Adeli K, Adolph TE, Adornetto A, Aflaki E, Agam G, Agarwal A, Aggarwal BB, Agnello M, Agostinis P, Agrewala JN, Agrotis A, Aguilar PV, Ahmad ST, Ahmed ZM, Ahumada-Castro U, Aits S, Aizawa S, Akkoc Y, Akoumianaki T, Akpinar HA, Al-Abd AM, Al-Akra L, Al-Gharaibeh A, Alaoui-Jamali MA, Alberti S, Alcocer-Gómez E, Alessandri C, Ali M, Alim Al-Bari MA, Aliwaini S, Alizadeh J, Almacellas E, Almasan A, Alonso A, Alonso GD, Altan-Bonnet N, Altieri DC, Álvarez ÉMC, Alves S, Alves da Costa C, Alzaharna MM, Amadio M, Amantini C, Amaral C, Ambrosio S, Amer AO, Ammanathan V, An Z, Andersen SU, Andrabi SA, Andrade-Silva M, Andres AM, Angelini S, Ann D, Anozie UC, Ansari MY, Antas P, Antebi A, Antón Z, Anwar T, Apetoh L, Apostolova N, Araki T, Araki Y, Arasaki K, Araújo WL, Araya J, Arden C, Arévalo MA, Arguelles S, Arias E, Arikkath J, Arimoto H, Ariosa AR, Armstrong-James D, Arnauné-Pelloquin L, Aroca A, Arroyo DS, Arsov I, Artero R, Asaro DML, Aschner M, Ashrafizadeh M, Ashur-Fabian O, Atanasov AG, Au AK, Auberger P, Auner HW, Aurelian L, Autelli R, Avagliano L, Ávalos Y, Aveic S, Aveleira CA, Avin-Wittenberg T, Aydin Y, Ayton S, Ayyadevara S, Azzopardi M, Baba M, Backer JM, Backues SK, Bae DH, Bae ON, Bae SH, Baehrecke EH, Baek A, Baek SH, Baek SH, Bagetta G, Bagniewska-Zadworna A, Bai H, Bai J, Bai X, Bai Y, Bairagi N, Baksi S, Balbi T, Baldari CT, Balduini W, Ballabio A, Ballester M, Balazadeh S, Balzan R, Bandopadhyay R, Banerjee S, Banerjee S, Bánréti Á, Bao Y, Baptista MS, Baracca A, Barbati C, Bargiela A, Barilà D, Barlow PG, Barmada SJ, Barreiro E, Barreto GE, Bartek J, Bartel B, Bartolome A, Barve GR, Basagoudanavar SH, Bassham DC, Bast RC, Basu A, Batoko H, Batten I, Baulieu EE, Baumgarner BL, Bayry J, Beale R, Beau I, Beaumatin F, Bechara LRG, Beck GR, Beers MF, Begun J, Behrends C, Behrens GMN, Bei R, Bejarano E, Bel S, Behl C, Belaid A, Belgareh-Touzé N, Bellarosa C, Belleudi F, Belló Pérez M, Bello-Morales R, Beltran JSO, Beltran S, Benbrook DM, Bendorius M, Benitez BA, Benito-Cuesta I, Bensalem J, Berchtold MW, Berezowska S, Bergamaschi D, Bergami M, Bergmann A, Berliocchi L, Berlioz-Torrent C, Bernard A, Berthoux L, Besirli CG, Besteiro S, Betin VM, Beyaert R, Bezbradica JS, Bhaskar K, Bhatia-Kissova I, Bhattacharya R, Bhattacharya S, Bhattacharyya S, Bhuiyan MS, Bhutia SK, Bi L, Bi X, Biden TJ, Bijian K, Billes VA, Binart N, Bincoletto C, Birgisdottir AB, Bjorkoy G, Blanco G, Blas-Garcia A, Blasiak J, Blomgran R, Blomgren K, Blum JS, Boada-Romero E, Boban M, Boesze-Battaglia K, Boeuf P, Boland B, Bomont P, Bonaldo P, Bonam SR, Bonfili L, Bonifacino JS, Boone BA, Bootman MD, Bordi M, Borner C, Bornhauser BC, Borthakur G, Bosch J, Bose S, Botana LM, Botas J, Boulanger CM, Boulton ME, Bourdenx M, Bourgeois B, Bourke NM, Bousquet G, Boya P, Bozhkov PV, Bozi LHM, Bozkurt TO, Brackney DE, Brandts CH, Braun RJ, Braus GH, Bravo-Sagua R, Bravo-San Pedro JM, Brest P, Bringer MA, Briones-Herrera A, Broaddus VC, Brodersen P, Brodsky JL, Brody SL, Bronson PG, Bronstein JM, Brown CN, Brown RE, Brum PC, Brumell JH, Brunetti-Pierri N, Bruno D, Bryson-Richardson RJ, Bucci C, Buchrieser C, Bueno M, Buitrago-Molina LE, Buraschi S, Buch S, Buchan JR, Buckingham EM, Budak H, Budini M, Bultynck G, Burada F, Burgoyne JR, Burón MI, Bustos V, Büttner S, Butturini E, Byrd A, Cabas I, Cabrera-Benitez S, Cadwell K, Cai J, Cai L, Cai Q, Cairó M, Calbet JA, Caldwell GA, Caldwell KA, Call JA, Calvani R, Calvo AC, Calvo-Rubio Barrera M, Camara NO, Camonis JH, Camougrand N, Campanella M, Campbell EM, Campbell-Valois FX, Campello S, Campesi I, Campos JC, Camuzard O, Cancino J, Candido de Almeida D, Canesi L, Caniggia I, Canonico B, Cantí C, Cao B, Caraglia M, Caramés B, Carchman EH, Cardenal-Muñoz E, Cardenas C, Cardenas L, Cardoso SM, Carew JS, Carle GF, Carleton G, Carloni S, Carmona-Gutierrez D, et al

A Mitochondrial tRNA Mutation Causes Axonal CMT in a Large Venezuelan Family.

Annals of neurology

Fay A, Garcia Y, Margeta M, Maharjan S, Jürgensen C, Briceño J, Garcia M, Yin S, Bassaganyas L, McMahon T, Hou YM, Fu YH, Ptácek LJ

Educational Case: Mitochondrial Myopathy.

Academic pathology

Lucas CG, Margeta M

Neuroglial stem cell-derived inflammatory pseudotumor (n-SCIPT): clinicopathologic characterization of a novel lesion of the lumbosacral spinal cord and nerve roots following intrathecal allogeneic stem cell intervention.

Acta neuropathologica

Sloan EA, Sampognaro PJ, Junn JC, Chin C, Jacques L, Ramachandran PS, DeRisi JL, Wilson MR, Kriegstein AR, Bollen AW, Solomon DA, Margeta M, Engstrom JW

Autophagy Defects in Skeletal Myopathies.

Annual review of pathology

Margeta M

COL4A1 Mutations Cause Neuromuscular Disease with Tissue-Specific Mechanistic Heterogeneity.

American journal of human genetics

Labelle-Dumais C, Schuitema V, Hayashi G, Hoff K, Gong W, Dao DQ, Ullian EM, Oishi P, Margeta M, Gould DB

Skeletal myopathy in Pompe disease: a failure of satellite cell activation?

Acta neuropathologica communications

Hiniker A, Margeta M

Activation of the Keap1/Nrf2 stress response pathway in autophagic vacuolar myopathies.

Acta neuropathologica communications

Duleh S, Wang X, Komirenko A, Margeta M

T-Cell-Mediated Inflammatory Myopathies in HIV-Positive Individuals: A Histologic Study of 19 Cases.

Journal of neuropathology and experimental neurology

Hiniker A, Daniels BH, Margeta M

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).

Autophagy

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, Adhihetty PJ, Adler SG, Agam G, Agarwal R, Aghi MK, Agnello M, Agostinis P, Aguilar PV, Aguirre-Ghiso J, Airoldi EM, Ait-Si-Ali S, Akematsu T, Akporiaye ET, Al-Rubeai M, Albaiceta GM, Albanese C, Albani D, Albert ML, Aldudo J, Algül H, Alirezaei M, Alloza I, Almasan A, Almonte-Beceril M, Alnemri ES, Alonso C, Altan-Bonnet N, Altieri DC, Alvarez S, Alvarez-Erviti L, Alves S, Amadoro G, Amano A, Amantini C, Ambrosio S, Amelio I, Amer AO, Amessou M, Amon A, An Z, Anania FA, Andersen SU, Andley UP, Andreadi CK, Andrieu-Abadie N, Anel A, Ann DK, Anoopkumar-Dukie S, Antonioli M, Aoki H, Apostolova N, Aquila S, Aquilano K, Araki K, Arama E, Aranda A, Araya J, Arcaro A, Arias E, Arimoto H, Ariosa AR, Armstrong JL, Arnould T, Arsov I, Asanuma K, Askanas V, Asselin E, Atarashi R, Atherton SS, Atkin JD, Attardi LD, Auberger P, Auburger G, Aurelian L, Autelli R, Avagliano L, Avantaggiati ML, Avrahami L, Awale S, Azad N, Bachetti T, Backer JM, Bae DH, Bae JS, Bae ON, Bae SH, Baehrecke EH, Baek SH, Baghdiguian S, Bagniewska-Zadworna A, Bai H, Bai J, Bai XY, Bailly Y, Balaji KN, Balduini W, Ballabio A, Balzan R, Banerjee R, Bánhegyi G, Bao H, Barbeau B, Barrachina MD, Barreiro E, Bartel B, Bartolomé A, Bassham DC, Bassi MT, Bast RC, Basu A, Batista MT, Batoko H, Battino M, Bauckman K, Baumgarner BL, Bayer KU, Beale R, Beaulieu JF, Beck GR, Becker C, Beckham JD, Bédard PA, Bednarski PJ, Begley TJ, Behl C, Behrends C, Behrens GM, Behrns KE, Bejarano E, Belaid A, Belleudi F, Bénard G, Berchem G, Bergamaschi D, Bergami M, Berkhout B, Berliocchi L, Bernard A, Bernard M, Bernassola F, Bertolotti A, Bess AS, Besteiro S, Bettuzzi S, Bhalla S, Bhattacharyya S, Bhutia SK, Biagosch C, Bianchi MW, Biard-Piechaczyk M, Billes V, Bincoletto C, Bingol B, Bird SW, Bitoun M, Bjedov I, Blackstone C, Blanc L, Blanco GA, Blomhoff HK, Boada-Romero E, Böckler S, Boes M, Boesze-Battaglia K, Boise LH, Bolino A, Boman A, Bonaldo P, Bordi M, Bosch J, Botana LM, Botti J, Bou G, Bouché M, Bouchecareilh M, Boucher MJ, Boulton ME, Bouret SG, Boya P, Boyer-Guittaut M, Bozhkov PV, Brady N, Braga VM, Brancolini C, Braus GH, Bravo-San Pedro JM, Brennan LA, Bresnick EH, Brest P, Bridges D, Bringer MA, Brini M, Brito GC, Brodin B, Brookes PS, Brown EJ, Brown K, Broxmeyer HE, Bruhat A, Brum PC, Brumell JH, Brunetti-Pierri N, Bryson-Richardson RJ, Buch S, Buchan AM, Budak H, Bulavin DV, Bultman SJ, Bultynck G, Bumbasirevic V, Burelle Y, Burke RE, Burmeister M, Bütikofer P, Caberlotto L, Cadwell K, Cahova M, Cai D, Cai J, Cai Q, Calatayud S, Camougrand N, Campanella M, Campbell GR, Campbell M, Campello S, Candau R, Caniggia I, Cantoni L, Cao L, Caplan AB, Caraglia M, Cardinali C, Cardoso SM, Carew JS, Carleton LA, Carlin CR, Carloni S, Carlsson SR, Carmona-Gutierrez D, Carneiro LA, Carnevali O, Carra S, Carrier A, Carroll B, Casas C, Casas J, Cassinelli G, Castets P, Castro-Obregon S, Cavallini G, Ceccherini I, Cecconi F, Cederbaum AI, Ceña V, Cenci S, Cerella C, Cervia D, Cetrullo S, Chaachouay H, Chae HJ, Chagin AS, Chai CY, Chakrabarti G, Chamilos G, Chan EY, Chan MT, Chandra D, Chandra P, Chang CP, Chang RC, Chang TY, Chatham JC, Chatterjee S, Chauhan S, Che Y, Cheetham ME, Cheluvappa R, Chen CJ, Chen G, Chen GC, Chen G, Chen H, Chen JW, Chen JK, Chen M, Chen M, Chen P, Chen Q, Chen Q, Chen SD, Chen S, Chen SS, Chen W, Chen WJ, Chen WQ, Chen W, Chen X, Chen YH, Chen YG, Chen Y, Chen Y, Chen Y, Chen YJ, Chen YQ, Chen Y, Chen Z, Chen Z, Cheng A, Cheng CH, Cheng H, Cheong H, Cherry S, Chesney J, Cheung CH, Chevet E, Chi HC, Chi SG, Chiacchiera F, Chiang HL, Chiarelli R, Chiariello M, Chieppa M, Chin LS, Chiong M, Chiu GN, Cho DH, Cho SG, Cho WC, Cho YY, Cho YS, Choi AM, Choi EJ, Choi EK, Choi J, Choi ME, Choi SI, Chou TF, Chouaib S, Choubey D, Choubey V, Chow KC, Chowdhury K, Chu CT, Chuang TH, Chun T, Chung H, Chung T, Chung YL, Chwae YJ, Cianfanelli V, et al

Sarcoid polyneuropathy masquerading as chronic inflammatory demyelinating polyneuropathy.

Muscle & nerve

Singhal NS, Irodenko VS, Margeta M, Layzer RB

Complex sarcolemmal invaginations mimicking myotendinous junctions in a case of Laing early-onset distal myopathy.

Neuropathology : official journal of the Japanese Society of Neuropathology

Reis GF, de la Motte G, Gooding R, Laing NG, Margeta M

Astrocytes increase the activity of synaptic GluN2B NMDA receptors.

Frontiers in cellular neuroscience

Hahn J, Wang X, Margeta M

Amyloid polyneuropathy caused by wild-type transthyretin.

Muscle & nerve

Lam L, Margeta M, Layzer R

CNS intravascular large cell lymphoma in a patient with autoimmune hemolytic anemia.

Neuropathology : official journal of the Japanese Society of Neuropathology

Alexandrescu S, Orengo JP, Toossi S, Perry A, Treseler P, Hess C, Margeta M

Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy.

Science translational medicine

Villalta SA, Rosenthal W, Martinez L, Kaur A, Sparwasser T, Tidball JG, Margeta M, Spencer MJ, Bluestone JA

Analysis of Mll1 deficiency identifies neurogenic transcriptional modules and Brn4 as a factor for direct astrocyte-to-neuron reprogramming.

Neurosurgery

Potts MB, Siu JJ, Price JD, Salinas RD, Cho MJ, Ramos AD, Hahn J, Margeta M, Oldham MC, Lim DA

Axial mitochondrial myopathy in a patient with rapidly progressive adult-onset scoliosis.

Acta neuropathologica communications

Hiniker A, Wong LJ, Berven S, Truong CK, Adesina AM, Margeta M

Novel interstitial 2.6 Mb deletion on 9q21 associated with multiple congenital anomalies.

American journal of medical genetics. Part A

Pua HH, Krishnamurthi S, Farrell J, Margeta M, Ursell PC, Powers M, Slavotinek AM, Jeng LJ

Increased autophagy accelerates colchicine-induced muscle toxicity.

Autophagy

Ching JK, Ju JS, Pittman SK, Margeta M, Weihl CC

The CHC22 clathrin-GLUT4 transport pathway contributes to skeletal muscle regeneration.

PloS one

Hoshino S, Sakamoto K, Vassilopoulos S, Camus SM, Griffin CA, Esk C, Torres JA, Ohkoshi N, Ishii A, Tamaoka A, Funke BH, Kucherlapati R, Margeta M, Rando TA, Brodsky FM

Neuronal activity regulates astrocytic Nrf2 signaling.

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

Habas A, Hahn J, Wang X, Margeta M

LC3 and p62 as diagnostic markers of drug-induced autophagic vacuolar cardiomyopathy: a study of 3 cases.

The American journal of surgical pathology

Daniels BH, McComb RD, Mobley BC, Gultekin SH, Lee HS, Margeta M

Rare somatic cells from human breast tissue exhibit extensive lineage plasticity.

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

Roy S, Gascard P, Dumont N, Zhao J, Pan D, Petrie S, Margeta M, Tlsty TD

Cardiac pathology exceeds skeletal muscle pathology in two cases of limb-girdle muscular dystrophy type 2I.

Muscle & nerve

Margeta M, Connolly AM, Winder TL, Pestronk A, Moore SA

Dermatomyositis with inclusion body myositis pathology.

Muscle & nerve

Layzer R, Lee HS, Iverson D, Margeta M

Cardiac pathology in a case of limb-girdle muscular dystrophy type 2I (LGMD-2I).

The FASEB Journal

Marta Margeta, Thomas L Winder, Steven A Moore

Type B gamma-aminobutyric acid receptors modulate the function of the extracellular Ca2+-sensing receptor and cell differentiation in murine growth plate chondrocytes.

Endocrinology

Cheng Z, Tu C, Rodriguez L, Chen TH, Dvorak MM, Margeta M, Gassmann M, Bettler B, Shoback D, Chang W

Complex formation with the Type B gamma-aminobutyric acid receptor affects the expression and signal transduction of the extracellular calcium-sensing receptor. Studies with HEK-293 cells and neurons.

The Journal of biological chemistry

Chang W, Tu C, Cheng Z, Rodriguez L, Chen TH, Gassmann M, Bettler B, Margeta M, Jan LY, Shoback D

Infant botulism, type F, presenting at 54 hours of life.

Pediatric neurology

Keet CA, Fox CK, Margeta M, Marco E, Shane AL, Dearmond SJ, Strober JB, Miller SP

Contribution of GIRK2-mediated postsynaptic signaling to opiate and alpha 2-adrenergic analgesia and analgesic sex differences.

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

Mitrovic I, Margeta-Mitrovic M, Bader S, Stoffel M, Jan LY, Basbaum AI

Function of GB1 and GB2 subunits in G protein coupling of GABA(B) receptors.

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

Margeta-Mitrovic M, Jan YN, Jan LY

Ligand-induced signal transduction within heterodimeric GABA(B) receptor.

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

Margeta-Mitrovic M, Jan YN, Jan LY

Immunohistochemical localization of GABA(B) receptors in the rat central nervous system.

The Journal of comparative neurology

Margeta-Mitrovic M, Mitrovic I, Riley RC, Jan LY, Basbaum AI

Neurotensin and substance P inhibit low- and high-voltage-activated Ca2+ channels in cultured newborn rat nucleus basalis neurons.

Journal of neurophysiology

Margeta-Mitrovic M, Grigg JJ, Koyano K, Nakajima Y, Nakajima S