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Division of Neuropathology

Email ceberha@jhmi.edu
Phone (410) 502-5185

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Opthalmic Pathology

Charles G. Eberhart, M.D., Ph.D.

Director, Division of Neuropathology
Primary Appointment in Pathology
Member, Graduate Program in Pathobiology

My research focuses on the pathology and genetics of brain and eye tumors. We have studied the role played by the Wnt, Notch and Hedgehog pathways in medulloblastoma and other embryonal tumors as well as malignant gliomas and uveal melanoma. These pathways regulate neural stem cell identity, and we have shown that Notch and Hedgehog are required in stem-like malignant glioma and medulloblastoma cells (“cancer stem cells”) as well. Our demonstration that pharmacological inhibition of either Notch or Hedgehog activity depletes stem-like cells from tumor cultures and slows or prevents clonogenic growth and xenograft initiation has helped to provide a rational for trials of Notch and Hedgehog inhibitors currently underway in children and adults. We also work on the effects of hypoxia, the pathobiology of low grade gliomas in the brain, and melanomas in the eye. I practice as a diagnostic pathologist, and pursue clinical/translational studies in which we seek to associate molecular changes in tumors with pathological subtype or clinical outcome.

Rodriguez FJ, Orr BA, Ligon KL, Eberhart CG. Neoplastic cells are a rare component in human glioblastoma microvasculature. Oncotarget 2012;3:98-106.

Asnaghi L, Ebrahimi KB, Schreck KC, Bar EE, Coonfield ML, Bell WR, Handa J, Merbs SL, Harbour JW, Eberhart CG. Notch signaling promotes growth and invasion in uveal melanoma. Clin Cancer Res 2012;18(3):654-65.

Chu Q, Orr BA, Semenkow S, Bar EE, Eberhart CG. Prolonged Inhibition of Glioblastoma Xenograft Initiation and Clonogenic Growth following In Vivo Notch Blockade. Clin Cancer Res 2013;19(12):3224-33.

Rajaii F, Asnaghi L, Enke R, Merbs SL, Handa JT, Eberhart CG. The demethylating agent 5-Aza reduces the growth, invasiveness, and clonogenicity of uveal and cutaneous melanoma. Invest Ophthalmol Vis Sci 2014;55(10):6178-86.

Asnaghi L, Lin MH, Lim KS, Lim KJ, Tripathy A, Wendeborn M, Merbs SL, Handa JT, Sodhi A, Bar EE, Eberhart CG. Hypoxia promotes uveal melanoma invasion through enhanced Notch and MAPK activation. PLoS One. 2014;9(8):e105372. PMCID: PMC4148307

Kahlert UD, Suwala AK, Raabe EH, Siebzehnrubi FA, Suarez MJ, Orr BA, Bar EE, Maciaczyk J, Eberhart CG. ZEB1 promotes invasion in human fetal neural stem cells and hypoxic glioma neurospheres. Brain Pathol 2014 Dec 17. [Epub ahead of print]. PMID: 25521330

Lim KJ, Brandt WD, Heth JA, Muraszko KM, Fan X, Bar EE, Eberhart CG. Lateral inhibition of Notch signaling in neoplastic cells. Oncotarget 2015 Jan 30;6(3):1666-77. PMID: 25557173

Kahlert UD, Suwala AK, Koch K, Natsumeda M, Orr BA, Hayashi M, Maciaczyk J, Eberhart CG. Pharmacologic Wnt Inhibition Reduces Proliferation, Survival, and Clonogenicity of Glioblastoma Cells. J Neuropathol Exp Neurol. 2015 Sep;74(9):889-900

Kahlert UD, Cheng M, Koch K, Marchionni L, Fan X, Raabe EH, Maciaczyk J, Glunde K, Eberhart CG. Alterations in cellular metabolome after pharmacological inhibition of Notch in glioblastoma cells. Int J Cancer. 2015 Sep 30. Epub ahead of print.

Email lchen99@jhu.edu
Phone (410) 955-8102
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Liam L. Chen, M.D., Ph.D.

Primary Appointment in Pathology

My research interests focus on understanding the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. We use Drosophila, fruit fly, as a model to study the mechanisms underlying central nervous system malfunction in humans. We express pathological human genes in the fly to generate an abnormal phenotype, such as age-dependent learning and memory defect, slowed motor activity, neuronal or glial cell loss. This phenotype can then be used in conjunction with the rich genetic toolbox that Drosophila researchers have developed to identify pathways that contribute to this degeneration. Their small size, rapid generation time, and low costs for maintenance make fruit flies ideal for studying neurodegenerative disease. The Drosophila models provide a platform for genome-wide screens and unbiased genetic screens to identify components of pathological pathways.

Chen L, Periquet M, Wang X, Negro A, McLean PJ, Hyman BT, Feany MB. Tyrosine and serine phosphorylation of alpha-synuclein have opposing effects on neurotoxicity and soluble oligomer formation. J Clin Invest. 2009. 119(11):3257-65.

Nosho K, Shima K, Irahara N, Kure S, Firestein R, Baba Y, Toyoda S, Chen L, Hazra A, Giovannucci EL, Fuchs CS, Ogino S. SIRT1 histone deacetylase expression is associated with microsatellite instability and CpG island methylator phenotype in colorectal cancer. Mod Pathol. 2009. 22(7):922-32.

Chen L, Feany MB. Alpha-synuclein phosphorylation controls neurotoxicity and inclusion formation in a Drosophila model of Parkinson disease. Nat Neurosci. 2005. 8(5):657-63.

Chen L, O'Keefe SL, Hodgetts RB. Control of Dopa decarboxylase gene expression by the Broad-Complex during metamorphosis in Drosophila. Mech Dev. 2002. 119(2):145-56.

Email koliat@jhmi.edu
Phone (410) 502-5172

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Koliatsos Laboratory

Traumatic Brain Injury Research Center

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Vassilis E. Koliatsos, M.D.

Primary Appointment in Pathology; Secondary Appointments in Neurology, Neuroscience, Psychiatry
Member, Graduate Program in Neuroscience; Member, Graduate Program in Pathobiology

Vassilis E. Koliatsos, MD, MBA is Professor of Pathology (Neuropathology) and Neurology and Associate Professor of Psychiatry and Behavioral Sciences. His main research interest is neural responses to traumatic and degenerative insults and mechanisms of neural repair and has close to 100 publications in this area. He has characterized a number of nourishing peptide chemicals (“neurotrophic factors”) for key populations of neurons in the brain and his stem cell work in animal models of disease has recently entered the first clinical trial of cellular therapy for a major neurodegenerative disorder (ALS). He has mentored numerous pre- and post-doctoral students and has taught residents in neurology and psychiatry on basic and clinical neurosciences.

Dr. Koliatsos' present emphasis is on Traumatic Brain Injury (TBI), especially the role of axonopathy in mechanisms associated with chronic TBI such as disconnection and its transsynaptic effects, neuroinflammation, and proteinopathy (tauopathy, amyloidosis). In parallel, he does research on the use of stem cells as cellular therapies for TBI. He also explores the use of induced pluripotent stem cells as in vitro models (cell cultures, cerebral organoids) of human neurological and neuropsychiatric illness.

Dr. Koliatsos serves on the faculty of the Ph.D. graduate program of Pathobiology of Disease and has also served in the Ph.D. Neuroscience program. Dr. Koliatsos also leads the Traumatic Brain Injury Research Center in the Department of Pathology and sees patients with traumatic brain injury and degenerative dementias. Dr. Koliatsos has been awarded the Leadership and Excellence in Alzheimer’s disease Award and the Javits Neuroscience Investigator Award, both from NIH.


Xu L, Ryu J, Hiel H, Menon A, Aggarwal A, Rha E, Mahairaki V, Cummings BJ, Koliatsos VE: Transplantation of human oligodendrocyte progenitor cells in an animal model of diffuse traumatic axonal injury: survival and differentiation. Stem Cell Research and Therapy, in press

Sisniega A, Zbijewski W, Xu J, Dang H, Stayman J, Yorkston J, Aygun N, Koliatsos VE, Siewerdsen JH: High-fidelity artifact correction for cone-beam CT imaging of the brain. Physics in Medicine and Biology 60(4):1415-39, 2015.

Ryu J, Horkayne I, Plenticova O, Xu, L, Eberhart CG, Troncoso JC and Koliatsos VE: The problem of axonal injury in the brains of veterans with histories of blast exposure. Acta Neuropathol Commun. 2(1) 153; Nov 25, 2014.

Xu L, Nguyen J, Lehar M, Menon A, Rha E, Arena J, Ryu J, Marmarou C, Marsh-Armstrong N and Koliatsos VE: A mouse model of repeat mild traumatic brain injury: selective multifocal axonopathy, neuroinflammation, and neurodegeneration in the visual system. Exp Neurol. pii: S0014-4886(14)00364-1. 2014.

Mahairaki V, Ryu J., Peters A, Park TS, Burridge PW, Zambidis ET and Koliatsos VE: Transgene-free familial Alzheimer’s disease-derived iPSCs differentiate into mature neurons with pathogenic properties. Stem Cells Dev., 2014 Aug 21. [Epub ahead of print]

Rossi SL, Mahairaki V, Zhou L, Song Y, Koliatsos VE: Remodeling of piriform cortex after lesions in adult rodents. Neuroreport, 25(13):1006-1012, 2014.

Koliatsos VE, Cernak I, Xu L, Song Y, Savonenko A, Crain B, Eberhart CG, Frangakis CE, Melnikova T, Kim H, Lee D: A mouse model of blast injury to brain: initial pathological, neuropathological and behavioral characterization. J. Neuropathol. Exp. Neurol., 70(5):399-416, 2011.

Cernak I, Merkle AC, Koliatsos VE, Bilik J, Luong Q, Mahota T, Xu L, Slack N, Windle D and Ahmed FA: The pathobiology of blast injuries and blast-induced neurotrauma as identified using a new experimental model of injury in mice. Neurobiol. Dis., 41(2):538-51, 2011.

Nasonkin I, Mahairaki V, Xu L, Hatfield G, Cummings B, Eberhart C, Ryugo DK and Koliatsos VE: Long-term, stable differentiation of human embryonic stem cell-derived neural precursors grafted into the adult mammalian neostriatum. Stem Cells, 27(10): 2414-26, 2009.

Yan J, Xu L, Welsh AM, Hatfield G, Hazel T, Johe K, Koliatsos VE. Extensive neuronal differentiation of human neural stem cell grafts in adult rat spinal cord. PLoS Medicine, 4(2):318-332, 2007.

Xu L, Yan J, Chen D, Welsh AM , Hazel T, Johe K, Hatfield G , Koliatsos VE: Human neural stem cell grafts ameliorate motor neuron disease in SOD-1 transgenic rats. Transplantation, 82(7):865-875, 2006.

Email tli1@jhmi.edu
Phone (410) 502-5174
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Tong Li, Ph.D.

Primary Appointment in Pathology

My research is focused on understanding the molecular mechanisms of neurodegenerative disorders, such as Alzheimer’s Disease (AD). My general approach is to create and characterize transgenic and knockout mouse models to study disease mechanisms and test therapeutic strategies for human diseases.

AD is characterized pathologically by neuritic amyloid plaques and neurofibrillary tangles (NFT) in the brain. Genetic and pathophysiological studies indicate that abnormal accumulation of Aβ peptides, which is generated by sequential cleavage of APP by BACE1 and γ-secretase, plays a key role in AD. We have been focusing on understanding the function of γ-secretase in AD and other diseases. By generating and characterizing mice deleted for nicastrin, Aph-1a and Aph-1c (components of γ-secretase), we have demonstrated that these proteins are essential for γ-secretase activity. In addition, we found that partial reduction of γ-secretase activity significantly decreased the Aβ amyloid burden in mice, suggesting that γ-secretase can serve as a therapeutic target for AD. Currently, we are testing the efficacy of targeting γ-secretase using γ-secretase inhibitors and modulators, and the combination approach that target both BACE1 and γ-secretase for AD therapy.

Interestingly, we also found that Nct+/- mice and Nct+/-;PS1+/- mice develop skin tumors mainly around the head and neck area, which histopathologically resemble human head and neck squamous cell carcinoma (HNSCC). These observations led us to hypothesize that γ-secretase can serve as a tumor suppressor and mice with mutation in genes encoding γ-secretase may serve as useful models for the study of human HNSCC. In supporting this view, in a recent phase III clinical trial, individuals who took a γ-secretase inhibitor (Semagacestat, Eli Lilly) for a prolonged period of time developed skin tumors that resemble those observed in our mouse models, which highlighted the importance of using animal models for preclinical studies of new therapies for human diseases. Our further study will also provide a better understanding of the mechanisms whereby γ-secretase functions as a tumor suppressor, information that will provide insight into the development of new therapeutics for the treatment of AD and its related skin cancer.

Abnormal protein aggregation is a common pathologically feature of neurodegenerative disease. We are interested in understanding the pathological functions of protein aggregations in AD, such as neuritic plaques and NFT. NFT is consisted of hyperphosphorylated tau protein, which is observed not only in AD but also in other neurodegenerative diseases, such as FTD and TBI related dementia. The relationship between Aβ and tau pathologies during AD progression remains unclear. Recently, we have generated a mutant tau transgenic mouse line, in which four-repeat domain of human tau carrying the mutation ΔK280 (Tau4R-ΔK280) was conditionally expressed. By crossbreeding Tau4R-ΔK280 mice with a model of Aβ amyloidosis, APPswe;PS1ΔE9 mice, we generated mice that develop both Aβ and Tau pathologies. Using this model, we will further evaluate the relationship between these two lesions and mechanism-based therapies targeting both Aβ and tau. This new tau transgenic mouse model will also be used in studying the mechanisms and biomarkers of TBI related dementia.


Li T, Ma G, Cai H, Price DL, Wong PC. Nicastrin is required for assembly of presenilin/γ-secretase complexes to mediate Notch signaling and for processing and trafficking of β-amyloid precursor protein in mammals. J. Neuroscience. 23(8):3272-7, 2003

Li T, Wen H, Brayton C, Laird FM, Ma G, Peng S, Placanica L, Wu TC, Crain BJ, Price DL, Eberhart, CG, and Wong PC. Moderate reduction of γ-secretase attenuates amyloid burden and limits mechanism-based liabilities J. Neuroscience, 2007 27(40):10849-59

Li T, Wen H, Brayton C, Das P, Smithson LA, Fauq A, Fan X, Crain BJ, Price DL, Golde TE, Eberhart CG, Wong PC. EGFR and notch pathways participate in the tumor suppressor function of gamma -secretase. J Biol Chem. 2007, 282(44):32264–32273.

Chow VW, Savonenko, AV, Melnikova T, Kim H Price DL, Li T, and Wong PC. Modeling an anti-amyloid combination therapy for Alzheimer’s disease. Sci. Transl. Med. 2010. 2, 13ra1 PMCID:PMC2852193

Li T, Li Y, Ahn K, Price DL, Sisodia SS, Wong PC. Increased expression of PS1 is sufficient to elevate the level and activity of &gamma-secretase in vivo. Plos ONE. 2011, 6(11):e28179.

Email martinl@jhmi.edu
Phone (410) 502-5170
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Lee J. Martin, Ph.D.

Primary Appointment in Pathology; Secondary Appointment in Neuroscience
Member, Graduate Program in Neuroscience; Member, Graduate Program in Pathobiology

Mechanisms of Neuronal Death in Adult and Developing Central Nervous System. In the human central nervous system (CNS), neurons degenerate after acute neurological insults resulting from stroke and cardiac arrest and during the progression of adult-onset neurodegenerative diseases such as amyotrophic lateral sclerosis and Alzheimer's disease. Only certain groups of neurons degenerate in each of these neurological disorders, and this phenomenon is called selective vulnerability. In order to therapeutically manage and prevent this neurodegeneration, it is important to identify the cellular and molecular mechanisms of selective neuronal vulnerability and death. In my laboratory, we are testing the hypothesis that selective vulnerability is dictated by brain regional connectivity, mitochondrial function, and oxidative stress and is mediated by excitotoxic cell death resulting from abnormalities in excitatory, glutamatergic signal transduction pathways, including glutamate transporters and glutamate receptors as well as their downstream intracellular signaling molecules. We are also investigating the contribution of neuronal/glial apoptosis and necrosis as cell death pathways in animal (including transgenic mice) models of acute and progressive neurodegeneration. We use a variety of anatomical and molecular neurobiological approaches, including neuronal tract-tracing techniques, immunocytochemistry, immunoblotting, antipeptide antibody production, transmission electron microscopy, and DNA analysis to determine the precise regional and cellular vulnerabilities and the synaptic and molecular mechanisms that result in selective neuronal degeneration.

Martin LJ and Wong M. Aberrant regulation of DNA methylation in amyotrophic lateral sclerosis: A new target of disease mechanisms. Neurotherapeutics 10: 722-733, 2013.

Wong M, Gertz B, Chestnut BA and Martin LJ. Mitochondrial DNMT3A and DNA methylation in skeletal muscle and CNS of transgenic mouse models of ALS. Front. Cell. Neurosci. Dec 25;7:279. doi: 10.3389/fncel.2013.00279, 2013.

Martin LJ, Semenkow S, Hanaford A and Wong M. The mitochondrial permeability transition pore regulates Parkinson's disease development in mutant α-synuclein transgenic mice. Neurobiol. Aging 35:1132-1152, 2014.

Fayzullina A and Martin LJ. Skeletal muscle DNA damage precedes spinal motor neuron DNA damage in a mouse model of Spinal Muscular Atrophy (SMA). PLoS One. Mar 25;9(3):e93329. doi: 10.1371/journal.pone.0093329, 2014.

Martin LJ, Fancelli D, Wong M, Niedzwiecki M, Ballarini M, Plyte S and Chang Q. GNX-4728, a novel small molecule drug inhibitor of mitochondrial permeability transition, is therapeutic in a mouse model of amyotrophic lateral sclerosis. Front. Cell. Neurosci 8:433.doi: 10.3389/fncel.2014.00433, 2014.

Email tmelnik1@jhmi.edu
Phone (410) 502-2819
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Tatiana Melnikova, Ph.D.

Primary Appointment in Pathology

The main focus of our laboratory is the investigation of different animal models of Alzheimer's disease and the contribution of different Aβ species to the development of behavioral and cognitive deficits during disease progression. By using different experimental treatments or genetic manipulations to alter Aβ production, we analyze the reversibility of the cognitive deficits at different stages of disease. Animal models of familiar form of Alzheimer’s disease include conventional transgenic mouse models (APPswe,PS1dE9; APPswe/PS1dE9/Cox2, etc) and conditional mouse models ( APPsi:tTA). In the latter APP production is driven by a tetracycline transactivator expressed in the brain areas involved in learning and memory. The overexpression of APP transgene is modulated by tetracycline analog, doxycycline (DOX). In our recent study we demonstrated that acute suppression of new APPsi/Aβ production in the APPsi:tTa mice with high levels of plagues accumulation significantly improved performance in short-term spatial memory tasks. These changes upon continued suppression were transformed in further improvement in more demanding tasks that assess long-term spatial and working memories. However, deficits in episodic –like memory and cognitive flexibility were more persistent and were still present after three weeks of DOX treatment as well as high plaques burden. Cognitive improvements coincided with dramatic reduction of different APP metabolites (full-length APP, soluble APP ectodomains, and APP C-terminal fragments) at the end of experiment. Despite the fact that animal models couldn’t recapitulate all aspects of the human disease they allow us to dissect different stages of disease progression and define the sensitive periods when it is still possible to delay or reverse cognitive deficits.

In other projects we are looking at the pathogenic mechanisms involved in autism spectrum disorder and investigating the pathways implicated in schizophrenia-like endopenotypes. In particularly, we are studying BACE1- dependent NRG1-ErbB4 signaling interactions with glutamatergic receptors pathways. We found that the mice with deletion of BACE1 (-site APP cleavage enzyme1) exhibited multiple behavioral endophenotypes related to schizophrenia such as deficits in prepulse inhibition, novelty-induced hyperactivity, sensitivity to a psychostimulant, disturbances in social interactions, and cognitive deficits. We continue this work by testing the hypothesis that changes in BACE1/NRG1 signaling could be primary or secondary to the alterations in glutamatergic mechanisms implicated in schizophrenia. To this end, we compare two different models of schizophrenia. As a first model, we are using BACE1 knockout mice, in which changes in BACE1/NRG1 signaling are primary. In the second model we are using PCP treatment during early development that results in primary alterations in glutamatergic pathway.


Jankowsky JL, Melnikova T, Fadale DJ, Xu GM, Slunt HH, Gonzales V, Younkin LH, Younkin SG, Borchelt DR, Savonenko AV. Environmental enrichment mitigates cognitive deficits in a mouse model of Alzheimer's disease. The Journal of Neuroscience. 2005; 25: 5217-5224.

Savonenko AV, Xu GM, Melnikova T, Morton JL, Gonzales V, Wong M, Price D L, Tang F, Markowska AL, Borchelt DR. Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationship to β-amyloid deposition and neurotransmitter abnormalities. Neurobiology of Disease. 2005; 18: 602-617.

Email frodrig4@jhmi.edu
Phone (443) 287-6646
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Fausto J. Rodriguez, M.D.

Primary Appointment in Pathology; Secondary Appointment in Oncology

My clinical and research interests focus on the identification of diagnostic, prognostic, and therapeutic biomarkers in primary brain tumors. My current research activities aim to characterize molecular changes and signaling pathway alterations associated with the development of pediatric gliomas, as well as phenotypic characterization of murine models of CNS neoplasia. As part of a multidisciplinary effort, one of my main goals is to integrate classic histopathologic analyses with current ancillary and molecular data obtained through immunohistochemistry, microarray profiling, molecular cytogenetics, and genomic sequencing.


Rodriguez FJ, Gamez JD, Vrana JA, Theis JD, Giannini C, Scheithauer BW, Parisi J, Lucchinetti CF, Pendlebury WW, Dogan A. Immunoglobulin Derived Depositions in the Nervous System: Novel Mass Spectrometry Application for Protein characterization in Formalin-Fixed tissues. Lab Investig 2008;88:1024-37.

Rodriguez FJ, Giannini C, Asmann YW, Sharma MK, Perry A, Tibbetts KM, Jenkins RB, Scheithauer BW, Anant S, Jenkins S, Eberhart CG, Sarkaria JN, Gutmann DH. Gene Expression Profiling of NF1-associated and Sporadic Pilocytic Astrocytoma Identifies ALDH1L1 as an Underexpressed Candidate Biomarker in Aggressive Astrocytoma Subtypes. J Neuropathol Exp Neurol 2008;12:1194-1204

Bender AM, Collier LS, Rodriguez FJ, Tieu C, Larson JD, Halder C, Mahlum E,. Kollmeyer TM, Akagi K, Sarkar G, Largaespada DL, Jenkins RB. Sleeping Beauty-mediated somatic mutagenesis implicates Csf1 in the formation of high grade astrocytomas. Cancer Res 2010; 70:3557-65.

Rodriguez EF, Scheithauer BW, Giannini C, Rynearson A, Cen L, Hoesley B, Gilmer-Flynn H, Sarkaria JN, Jenkins S, Long J, Rodriguez FJ. PI3K/AKT Pathway Alterations are Associated With Clinically Aggressive and Histologically Anaplastic Subsets of Pilocytic Astrocytoma. Acta Neuropathol 2011;121:407-20.

Rodriguez FJ, Orr B, Ligon K, Eberhart CG. Neoplastic cells are a rare component in human glioblastoma microvasculature. Oncotarget 2012;3:98-106.

Email asavone1@jhmi.edu
Phone (410) 502-5196
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Alena V. Savonenko, Ph.D.

Primary Appointment in Pathology


Email troncoso@jhmi.edu
Phone (410) 502-5165
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Juan C. Troncoso, M.D.

Primary Appointment in Pathology; Secondary Appointment in Neurology
Member, Graduate Program in Pathobiology

Dr. Troncoso is Professor of Pathology and Neurology with Board-certifications in neurology and neuropathology. He received his M.D. from the Universidad Catolica de Chile, trained in clinical neurology at the Hahnemann Medical College and the Hospital of Philadelphia, and then in neuropathology at the Johns Hopkins School of Medicine. Dr. Troncoso directs a neuropathology research laboratory which is fully integrated with his service and teaching responsibilities.

The main research focus of the Troncoso laboratory is the pathology and neurobiology of age-associated neurological diseases, in particular the early and preclinical stages of Alzheimer’s disease. Dr. Troncoso directs the Neuropathology Cores for several NIH- and privately-funded research centers and studies at the Johns Hopkins University School of Medicine, including the Alzheimer’s Disease Research Center, the Udall Center for Excellence in Parkinson’s Research, the BIOCARD study, the Fronto-temporal Dementia Center, and the Baltimore Huntington’s Disease Center. A unique strength of Dr. Troncoso’s laboratory is the application of design-based stereology to the study of normal aging and neurodegenerative disorders both in humans and experimental animals.

Dr. Troncoso is also an expert in forensic neuropathology. He has been the neuropathology consultant to the Office of the Chief Medical Examiner for the State of Maryland since 1981. His experience in this field is collected in his book “Essential Forensic Neuropathology”, Lippincott Williams & Wilkins; 1st edition, 2009.

Research Funding. The Troncoso laboratory is funded from multiple sources that include NIA, NINDS, and private foundations. Dr. Troncoso is a recipient of a research grant from the BrightFocus Foundation entitled “Alzheimer’s Disease Pathology: before plaques and tangles”. This project focuses on degenerative neuropathology in subjects 30 to 50 years of age.

Teaching. Dr. Troncoso is a faculty member of the Pathobiology Graduate Program and is the director of the ACGME-accredited Fellowship training program in neuropathology. He is also PI of an R25 grant from NINDS that supports research training of neuropathology Fellows.


Dr. Troncoso is author of more than 250 publications. Below is a list of selected recent contributions:

Iacono D, Zandi P, Gross M, Markesbery W, Pletnikova O, Rudow G, Troncoso J. APOε2 and education in cognitively normal older subjects with high levels of AD pathology at autopsy: findings from the Nun Study. Oncotarget. 2015;6 (16):14082-91. PMCID: PMC4546453

Nucifora FC Jr, Nucifora LG, Ng CH, Arbez N, Guo Y, Roby E, Shani V, Engelender S, Wei D, Wang XF, Li T, Moore DJ, Pletnikova O, Troncoso JC, Sawa A, Dawson TM, Smith W, Lim KL, Ross CA. Ubiqutination via K27 and K29 chains signals aggregation and neuronal protection of LRRK2 by WSB1. Nat Commun. 2016;7:11792. PMCID:PMC4899630

Pletnikova O, Rudow GL, Hyde TM, Kleinman JE, Ali SZ, Bharadwaj R, Gangadeen S, Crain BJ, Fowler DR, Rubio AI, Troncoso JC. Alzheimer Lesions in the Autopsied Brains of People 30 to 50 Years of Age. Cogn Behav Neurol. 2015 Sep;28 (3):144-52. PMCID:PMC4588069

Bañez-Coronel M, Ayhan F, Tarabochia AD, Zu T, Perez BA, Tusi SK, Pletnikova O, Borchelt DR, Ross CA, Margolis RL, Yachnis AT, Troncoso JC, Ranum LP. RAN Translation in Huntington Disease. Neuron. 2015;88(4):667-77. PMCID:PMC4684947

Ling JP, Pletnikova O, Troncoso JC, Wong PC. NEURODEGENERATION. TDP-43 repression of nonconserved cryptic exons is compromised in ALS-FTD. Science. 2015;349(6248):650-5. PMCID: PMC4825810

Email WONG@jhmi.edu
Phone (410) 287-5689
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Philip C. Wong, Ph.D.

Primary Appointment in Pathology;
Joint Appointment in Neuroscience
Member, Graduate Program in Cellular and Molecular Medicine;
Member, Graduate Program in Neuroscience;
Member, Graduate Program in Pathobiology

Over the past 20 years, I have developed two major programs in the field of neurodegenerative diseases focused on molecular mechanisms of Alzheimer’s disease (AD) and Amyotrophic Lateral Sclerosis (ALS) and on defining the molecular participants potentially amendable to therapeutic interventions using molecular biological approaches, including transgenic and gene knockout strategies. Over the past decade, we assessed BACE1 and gamma-secretase, enzymes required for the generation of beta-amyloid, as therapeutic targets for AD. We are currently developing next generation set of mouse models of AD for mechanistic studies as well as for testing therapies. My laboratory also has built mouse models of motor neuron disease for the study of ALS. More recently, my group has generated mouse models of TDP-43 in efforts to unravel the physiology and pathophysiology of this RNA binding protein implicated in ALS and Frontotemporal dementia (FTD). We recently discovered a novel function of TDP-43 in repression of splicing of non-conserved cryptic exons and disclosed that this role of TDP-43 is compromised in brains of ALS-FTD. We currently are embarking on identifying functional biomarkers and validating repression of cryptic exons as a therapeutic target for ALS-FTD.

Chow VW, Savonenko AV, Melnikova T, Kim H, Price DL, Li T and Wong PC: Modeling an anti-amyloid combination therapy for Alzheimer's Disease. Science Translational Medicine 2:1-11, 2010. PMID 20371462 .

Chiang P-M, Ling J, Jeong YH, Price DL, Aja S and Wong PC: Deletion of TDP-43 down-regulates Tbc1d1, a gene linked to obesity, and alters body fat metabolism. Proc. Natl. Acad. Sci. USA 107: 16320-16324, 2010. PMID 20660762.

Shyam R, Ren Y, Lee J, Braunstein KE, Mao H-Q and Wong PC: Intraventricular delivery of siRNAs nanoparticles to the central nervous system. Molecular Therapy Nucleic Acids 4, e242, 2015 May 12.

Ling JP, Pletnikova O, Troncoso J and Wong PC: TDP-43 repression of non-conserved cryptic exons is compromised in ALS-FTD. Science 349:650-655, 2015. PMID 26250685.


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