Dr. Kratter is an adult psychiatrist and fellowship-trained neuropsychiatrist and Clinical Assistant Professor in the Department of Psychiatry & Behavioral Sciences at Stanford University School of Medicine. He is also director of Invasive Technologies in the Stanford Brain Stimulation Laboratory.

His clinical interests include the psychiatric and cognitive aspects of movement disorders like Parkinson's and Tourette's as well as depression, obsessive-compulsive disorder, and non-invasive and invasive neuromodulation for neuropsychiatric illness.

His research interests focus on assessing outcomes and understanding the mechanisms of both neuromodulatory and novel pharmacological treatments. This includes both clinical and more mechanistic studies, such as using techniques like repetitive transcranial magnetic stimulation (rTMS) and deep brain stimulation in combination with neuroimaging and electrophysiology. He has been a co-investigator for such studies focusing on obsessive-compulsive disorder, major depressive disorder, and suicidal ideation, and traumatic brain injury.
His work has appeared in a number of scientific journals including Nature Medicine, American Journal of Psychiatry, Journal of Clinical Investigation, Translational Psychiatry, and Proceedings of the National Academy of Science. He also co-authored the chapter on major depression in the textbook Deep Brain Stimulation: Techniques and Practice.

Clinical Focus

  • Psychiatry
  • Neuropsychiatry
  • Interventional Psychiatry

Academic Appointments

  • Clinical Assistant Professor, Psychiatry and Behavioral Sciences

Professional Education

  • Board Certification: American Osteopathic Board of Neurology and Psychiatry, Behavioral Neurology and Neuropsychiatry (2020)
  • Board Certification, United Council for Neurologic Subspecialties, Behavioral Neurology and Neuropsychiatry (2020)
  • Board Certification: American Board of Psychiatry and Neurology, Psychiatry (2019)
  • Fellowship: Stanford University Psychiatry and Behavioral Sciences (2020) CA
  • Residency: Western Psychiatric Institute and Clinic (2019) PA
  • Medical Education: University of California San Francisco Registrar Office (2015) CA

Clinical Trials

  • Accelerated Intermittent Theta-Burst Stimulation (aiTBS) in Treatment-Resistant Depression of Bipolar II Disorder Recruiting

    The purpose of this study is to investigate the effectiveness of accelerated intermittent theta-burst transcranial magnetic stimulation (aiTBS) in inducing anti-depressant responses in individuals with treatment-resistant depression of bipolar II disorder. This is a double-blind, randomized, sham-controlled trial that targets a single location on the left dorsolateral prefrontal cortex (LDLPFC) using the MagPro rTMS system.

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  • Neuroimaging Biomarkers for Predicting rTMS Response in OCD Recruiting

    This study evaluates an accelerated schedule of theta-burst stimulation using a Transcranial Magnetic Stimulation (TMS) device for treatment-resistant Obsessive Compulsive Disorder (OCD). In a randomized fashion, half the participants will receive accelerated theta-burst stimulation at the dorsomedial prefrontal cortex (DMPFC), while half will receive accelerated theta-burst stimulation at the right orbitofrontal (rOFC) site.

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  • Opiate Suicide Study in Patients With Major Depression Recruiting

    To explore whether intravenous ketamine followed by buprenorphine produces more rapid and sustained anti-suicidal effects than ketamine followed by placebo, investigators will conduct a single study that will take approximately 2.5 years to complete. 60 subjects (60 infusions) or approximately 24 infusions per year.

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  • Accelerated Theta Burst in Treatment-Resistant Depression: A Dose Finding and Biomarker Study Not Recruiting

    This study evaluates the effectiveness of re-treatment using accelerated schedule of intermittent theta-burst stimulation for treatment-resistant depression. This is an open label study.

    Stanford is currently not accepting patients for this trial. For more information, please contact Claudia Tischler, BA, 650-498-8535.

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  • Pilot Accelerated Theta Burst in Treatment-Resistant Bipolar Depression Not Recruiting

    This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial magnetic stimulation device for treatment-resistant bipolar depression. In this open-label study, all participants will receive accelerated theta-burst stimulation.

    Stanford is currently not accepting patients for this trial. For more information, please contact Nolan Williams, MD, 650-497-3933.

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All Publications

  • Causal network localization of brain stimulation targets for trait anxiety. Research square Siddiqi, S. H., Klingbeil, J., Webler, R., Kratter, I. H., Blumberger, D. M., Fox, M. D., George, M. S., Grafman, J. H., Pascual-Leone, A., Pines, A. R., Richardson, R. M., Talati, P., Vila-Rodriguez, F., Downar, J., Hershey, T., Black, K. J. 2024


    Transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS) can treat some neuropsychiatric disorders, but there is no consensus approach for identifying new targets. We localized causal circuit-based targets for anxiety that converged across multiple natural experiments. Lesions (n=451) and TMS sites (n=111) that modify anxiety mapped to a common normative brain circuit (r=0.68, p=0.01). In an independent dataset (n=300), individualized TMS site connectivity to this circuit predicted anxiety change (p=0.02). Subthalamic DBS sites overlapping the circuit caused more anxiety (n=74, p=0.006), thus demonstrating a network-level effect, as the circuit was derived without any subthalamic sites. The circuit was specific to trait versus state anxiety in datasets that measured both (p=0.003). Broadly, this illustrates a pathway for discovering novel circuit-based targets across neuropsychiatric disorders.

    View details for DOI 10.21203/

    View details for PubMedID 38659844

  • Pilot study of stanford neuromodulation therapy (SNT) for bipolar depression. Brain stimulation Raj, K. S., Geoly, A. D., Veerapal, C., Gholmieh, M., Toosi, P., Espil, F. M., Batail, J., Kratter, I. H., Williams, N. R. 2024

    View details for DOI 10.1016/j.brs.2024.03.002

    View details for PubMedID 38447774

  • Magnesium-ibogaine therapy in veterans with traumatic brain injuries. Nature medicine Cherian, K. N., Keynan, J. N., Anker, L., Faerman, A., Brown, R. E., Shamma, A., Keynan, O., Coetzee, J. P., Batail, J., Phillips, A., Bassano, N. J., Sahlem, G. L., Inzunza, J., Millar, T., Dickinson, J., Rolle, C. E., Keller, J., Adamson, M., Kratter, I. H., Williams, N. R. 2024


    Traumatic brain injury (TBI) is a leading cause of disability. Sequelae can include functional impairments and psychiatric syndromes such as post-traumatic stress disorder (PTSD), depression and anxiety. Special Operations Forces (SOF) veterans (SOVs) may be at an elevated risk for these complications, leading some to seek underexplored treatment alternatives such as the oneirogen ibogaine, a plant-derived compound known to interact with multiple neurotransmitter systems that has been studied primarily as a treatment for substance use disorders. Ibogaine has been associated with instances of fatal cardiac arrhythmia, but coadministration of magnesium may mitigate this concern. In the present study, we report a prospective observational study of the Magnesium-Ibogaine: the Stanford Traumatic Injury to the CNS protocol (MISTIC), provided together with complementary treatment modalities, in 30 male SOVs with predominantly mild TBI. We assessed changes in the World Health Organization Disability Assessment Schedule from baseline to immediately (primary outcome) and 1month (secondary outcome) after treatment. Additional secondary outcomes included changes in PTSD (Clinician-Administered PTSD Scale for DSM-5), depression (Montgomery-Asberg Depression Rating Scale) and anxiety (Hamilton Anxiety Rating Scale). MISTIC resulted in significant improvements in functioning both immediately (Pcorrected<0.001, Cohen's d=0.74) and 1month (Pcorrected< 0.001, d=2.20) after treatment and in PTSD (Pcorrected<0.001, d=2.54), depression (Pcorrected<0.001, d=2.80) and anxiety (Pcorrected<0.001, d=2.13) at 1month after treatment. There were no unexpected or serious adverse events. Controlled clinical trials to assess safety and efficacy are needed to validate these initial open-label findings. registration: NCT04313712 .

    View details for DOI 10.1038/s41591-023-02705-w

    View details for PubMedID 38182784

  • Sustained Efficacy of Stanford Neuromodulation Therapy (SNT) in Open-Label Repeated Treatment. The American journal of psychiatry Geoly, A. D., Kratter, I. H., Toosi, P., Cole, E. J., Sahlem, G. L., Williams, N. R. 2024; 181 (1): 71-73

    View details for DOI 10.1176/appi.ajp.20230113

    View details for PubMedID 38161297

  • A preliminary randomized controlled trial of repetitive transcranial magnetic stimulation applied to the left dorsolateral prefrontal cortex in treatment seeking participants with cannabis use disorder. Drug and alcohol dependence Sahlem, G. L., Kim, B., Baker, N. L., Wong, B. L., Caruso, M. A., Campbell, L. A., Kaloani, I., Sherman, B. J., Ford, T. J., Musleh, A. H., Kim, J. P., Williams, N. R., Manett, A. J., Kratter, I. H., Short, E. B., Killeen, T. K., George, M. S., McRae-Clark, A. L. 2023; 254: 111035


    Cannabis use disorder (CUD) is a common and consequential disorder. When applied to the dorsolateral prefrontal cortex (DLPFC), repetitive transcranial magnetic stimulation (rTMS) reduces craving across substance use disorders and may have therapeutic clinical effects when applied in serial-sessions. The present study sought to preliminarily determine whether serial-sessions of rTMS applied to the DLPFC had a therapeutic effect in CUD.This study was a two-site, phase-2, double-blind, randomized-controlled-trial. Seventy-two treatment-seeking participants (37.5% Women, mean age 30.2±9.9SD) with ≥moderate-CUD were randomized to active or sham rTMS (Beam-F3, 10Hz, 20-total-sessions, two-sessions-per-visit, two-visits-per-week, with cannabis cues) while undergoing a three-session motivational enhancement therapy intervention. The primary outcome was the change in craving between pre- and post- treatment (Marijuana Craving Questionnaire Short-Form-MCQ-SF). Secondary outcomes included the number of weeks of abstinence and the number of days-per-week of cannabis use during 4-weeks of follow-up.There were no significant differences in craving between conditions. Participants who received active-rTMS reported numerically, but not significantly, more weeks of abstinence in the follow-up period than those who received sham-rTMS (15.5%-Active; 9.3%-Sham; rate ratio = 1.66 [95% CI: 0.84, 3.28]; p=0.14). Participants who received active-rTMS reported fewer days-per-week of cannabis use over the final two-weeks of the follow-up period than those receiving sham-rTMS (Active vs. Sham: -0.72; Z=-2.33, p=0.02).This trial suggests rTMS is safe and feasible in individuals with CUD and may have a therapeutic effect on frequency of cannabis use, though further study is needed with additional rTMS-sessions and a longer follow-up period.

    View details for DOI 10.1016/j.drugalcdep.2023.111035

    View details for PubMedID 38043228

  • Responsive deep brain stimulation guided by ventral striatal electrophysiology of obsession durably ameliorates compulsion. Neuron Nho, Y. H., Rolle, C. E., Topalovic, U., Shivacharan, R. S., Cunningham, T. N., Hiller, S., Batista, D., Feng, A., Espil, F. M., Kratter, I. H., Bhati, M. T., Kellogg, M., Raslan, A. M., Williams, N. R., Garnett, J., Pesaran, B., Oathes, D. J., Suthana, N., Barbosa, D. A., Halpern, C. H. 2023


    Treatment-resistant obsessive-compulsive disorder (OCD) occurs in approximately one-third of OCD patients. Obsessions may fluctuate over time but often occur or worsen in the presence of internal (emotional state and thoughts) and external (visual and tactile) triggering stimuli. Obsessive thoughts and related compulsive urges fluctuate (are episodic) and so may respond well to a time-locked brain stimulation strategy sensitive and responsive to these symptom fluctuations. Early evidence suggests that neural activity can be captured from ventral striatal regions implicated in OCD to guide such a closed-loop approach. Here, we report on a first-in-human application of responsive deep brain stimulation (rDBS) of the ventral striatum for a treatment-refractory OCD individual who also had comorbid epilepsy. Self-reported obsessive symptoms and provoked OCD-related distress correlated with ventral striatal electrophysiology. rDBS detected the time-domain area-based feature from invasive electroencephalography low-frequency oscillatory power fluctuations that triggered bursts of stimulation to ameliorate OCD symptoms in a closed-loop fashion. rDBS provided rapid, robust, and durable improvement in obsessions and compulsions. These results provide proof of concept for a personalized, physiologically guided DBS strategy for OCD.

    View details for DOI 10.1016/j.neuron.2023.09.034

    View details for PubMedID 37865084

  • Network effects of Stanford Neuromodulation Therapy (SNT) in treatment-resistant major depressive disorder: a randomized, controlled trial. Translational psychiatry Batail, J., Xiao, X., Azeez, A., Tischler, C., Kratter, I. H., Bishop, J. H., Saggar, M., Williams, N. R. 2023; 13 (1): 240


    Here, we investigated the brain functional connectivity (FC) changes following a novel accelerated theta burst stimulation protocol known as Stanford Neuromodulation Therapy (SNT) which demonstrated significant antidepressant efficacy in treatment-resistant depression (TRD). In a sample of 24 patients (12 active and 12 sham), active stimulation was associated with significant pre- and post-treatment modulation of three FC pairs, involving the default mode network (DMN), amygdala, salience network (SN) and striatum. The most robust finding was the SNT effect on amygdala-DMN FC (group*time interaction F(1,22)=14.89, p<0.001). This FC change correlated with improvement in depressive symptoms (rho (Spearman) = -0.45, df=22, p=0.026). The post-treatment FC pattern showed a change in the direction of the healthy control group and was sustained at the one-month follow-up. These results are consistent with amygdala-DMN connectivity dysfunction as an underlying mechanism of TRD and bring us closer to the goal of developing imaging biomarkers for TMS treatment optimization.Trial registration: NCT03068715.

    View details for DOI 10.1038/s41398-023-02537-9

    View details for PubMedID 37400432

  • Targeted neurostimulation reverses a spatiotemporal biomarker of treatment-resistant depression. Proceedings of the National Academy of Sciences of the United States of America Mitra, A., Raichle, M. E., Geoly, A. D., Kratter, I. H., Williams, N. R. 2023; 120 (21): e2218958120


    Major depressive disorder (MDD) is widely hypothesized to result from disordered communication across brain-wide networks. Yet, prior resting-state-functional MRI (rs-fMRI) studies of MDD have studied zero-lag temporal synchrony (functional connectivity) in brain activity absent directional information. We utilize the recent discovery of stereotyped brain-wide directed signaling patterns in humans to investigate the relationship between directed rs-fMRI activity, MDD, and treatment response to FDA-approved neurostimulation paradigm termed Stanford neuromodulation therapy (SNT). We find that SNT over the left dorsolateral prefrontal cortex (DLPFC) induces directed signaling shifts in the left DLPFC and bilateral anterior cingulate cortex (ACC). Directional signaling shifts in the ACC, but not the DLPFC, predict improvement in depression symptoms, and moreover, pretreatment ACC signaling predicts both depression severity and the likelihood of SNT treatment response. Taken together, our findings suggest that ACC-based directed signaling patterns in rs-fMRI are a potential biomarker of MDD.

    View details for DOI 10.1073/pnas.2218958120

    View details for PubMedID 37186863

  • Depression history modulates effects of subthalamic nucleus topography on neuropsychological outcomes of deep brain stimulation for Parkinson's disease. Translational psychiatry Kratter, I. H., Jorge, A., Feyder, M. T., Whiteman, A. C., Chang, Y., Henry, L. C., Karp, J. F., Richardson, R. M. 2022; 12 (1): 213


    Patients with psychiatric symptoms, such as depression, anxiety, and visual hallucinations, may be at increased risk for adverse effects following deep brain stimulation of the subthalamic nucleus for Parkinson's disease, but there have been relatively few studies of associations between locations of chronic stimulation and neuropsychological outcomes. We sought to determine whether psychiatric history modulates associations between stimulation location within the subthalamic nucleus and postoperative affective and cognitive changes. We retrospectively identified 42 patients with Parkinson's disease who received bilateral subthalamic nucleus deep brain stimulation and who completed both pre- and postoperative neuropsychological testing. Active stimulation contacts were localized in MNI space using Lead-DBS software. Linear discriminant analysis identified vectors maximizing variance in postoperative neuropsychological changes, and Pearson's correlations were used to assess for linear relationships. Stimulation location was associated with postoperative change for only 3 of the 18 neuropsychological measures. Variation along the superioinferior (z) axis was most influential. Constraining the analysis to patients with a history of depression revealed 10 measures significantly associated with active contact location, primarily related to location along the anterioposterior (y) axis and with worse outcomes associated with more anterior stimulation. Analysis of patients with a history of anxiety revealed 5 measures with location-associated changes without a predominant axis. History of visual hallucinations was not associated with significant findings. Our results suggest that a history of depression may influence the relationship between active contact location and neuropsychological outcomes following subthalamic nucleus deep brain stimulation. These patients may be more sensitive to off-target (nonmotor) stimulation.

    View details for DOI 10.1038/s41398-022-01978-y

    View details for PubMedID 35624103

  • Lateralized Effect of Thalamic Deep Brain Stimulation Location on Verbal Abstraction. Movement disorders : official journal of the Movement Disorder Society Wang, D., Jorge, A., Lipski, W. J., Kratter, I. H., Henry, L. C., Richardson, R. M. 2021


    BACKGROUND: Regionalized thalamic activity has been implicated in language function, and yet the effect of thalamic deep brain stimulation (DBS) on language-related clinical outcomes is underexplored.OBJECTIVE: The objective of this study was to determine if the location of stimulation within the thalamus correlates with changes in language-related neuropsychological outcomes following DBS for essential tremor.METHODS: Thirty patients with essential tremor underwent comprehensive neuropsychological evaluations before and after DBS surgery targeting the ventral intermediate nucleus of the thalamus. Changes in neuropsychological functions were evaluated. The relationships between language-related outcomes and stimulation location were assessed using both categorical and linear methods. Any significant results were further validated using linear discriminant analysis.RESULTS: Most neuropsychological functions remained unchanged at the group level. However, outcome on a measure of verbal abstraction was significantly dependent on stimulation location along the anterior-posterior axis within the left ventral lateral thalamus, with anterior stimulation associated with reduced verbal abstraction performance. This result was supported by linear discriminant analysis, which showed that stimulation locations with improved and reduced verbal abstraction function were best separated by a vector nearly parallel to the anterior-posterior axis. No stimulation location dependence was found for verbal abstraction outcome in the right thalamus or for outcomes of other language functions in either hemisphere.CONCLUSION: We demonstrate an effect of thalamic DBS on verbal abstraction as a function of left thalamic topography. This finding provides clinical evidence for the lateralization and regionalization of thalamic language function that may be relevant for understanding nonmotor effects of stimulation. © 2021 International Parkinson and Movement Disorder Society.

    View details for DOI 10.1002/mds.28606

    View details for PubMedID 33818819

  • Can (or Should) We Treat Depression and Anxiety in Parkinson's Disease Algorithmically? The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry Martyna, M. R., Trapp, N. T., Kratter, I. H. 2021

    View details for DOI 10.1016/j.jagp.2021.03.001

    View details for PubMedID 33824056

  • Association of Preoperative Visual Hallucinations With Cognitive Decline After Deep Brain Stimulation for Parkinson's Disease. The Journal of neuropsychiatry and clinical neurosciences Kratter, I. H., Karp, J. F., Chang, Y., Whiteman, A. C., Feyder, M. T., Jorge, A., Richardson, R. M., Henry, L. C. 2020: appineuropsych20040077


    OBJECTIVE: Deep brain stimulation (DBS) is effective for the motor symptoms of Parkinson's disease (PD). Although most patients benefit with minimal cognitive side effects, cognitive decline is a risk, and there is little available evidence to guide preoperative risk assessment. Visual illusions or visual hallucinations (VHs) and impulse-control behaviors (ICBs) are relatively common complications of PD and its treatment and may be a marker of more advanced disease, but their relationship with postoperative cognition has not been established. The authors aimed to determine whether any preoperative history of VHs or ICBs is associated with cognitive change after DBS.METHODS: Retrospective chart review identified 54 patients with PD who received DBS of the subthalamic nucleus or globus pallidus internus and who completed both pre- and postoperative neuropsychological testing. Linear regression models were used to assess whether any preoperative history of VHs or ICBs was associated with changes in attention, executive function, language, memory, or visuospatial cognitive domains while controlling for surgical target and duration between evaluations.RESULTS: The investigators found that a history of VHs was associated with declines in attention (b=-4.04, p=0.041) and executive function (b=-4.24, p=0.021). A history of ICBs was not associated with any significant changes.CONCLUSIONS: These results suggest that a history of VHs may increase risk of cognitive decline after DBS; thus, specific preoperative counseling and targeted remediation strategies for these patients may be indicated. In contrast, a history of ICBs does not appear to be associated with increased cognitive risk.

    View details for DOI 10.1176/appi.neuropsych.20040077

    View details for PubMedID 33203305

  • Anterior Sensorimotor Subthalamic Nucleus Stimulation Is Associated With Improved Voice Function. Neurosurgery Jorge, A., Dastolfo-Hromack, C., Lipski, W. J., Kratter, I. H., Smith, L. J., Gartner-Schmidt, J. L., Richardson, R. M. 2020


    BACKGROUND: Despite the impact of Parkinson disease (PD) on speech communication, there is no consensus regarding the effect of lead location on voice-related outcomes in subthalamic nucleus (STN) deep brain stimulation (DBS).OBJECTIVE: To determine the relationship of stimulation location to changes in cepstral analyses of voice following STN DBS.METHODS: Speech pathology evaluations were obtained from 14 PD subjects, before and after STN DBS, including audio-perceptual voice ratings (overall severity, loudness, hoarseness changes), measured indices of dysphonia (cepstral peak prominence and cepstral spectral index of dysphonia), and phonatory aerodynamics. The contact locations used for active stimulation at the time of postoperative voice evaluations were determined and assessed in relation to voice outcomes.RESULTS: Voice outcomes remained relatively unchanged on average. Stimulation locations in the anterior portion of the sensorimotor region of the left STN, however, were associated with improvements in voice severity scores, cepstral spectral index of dysphonia, shortness of breath, and phonatory airflow during connected speech. Posterior locations were associated with worsening of these outcomes. Variation in the medial-lateral or dorsal-ventral position on the left, and in any direction on the right, did not correlate with any voice outcome.CONCLUSION: Active contact placement within the anterior sensorimotor STN was associated with improved perceptual and acoustic-aerodynamic voice-related outcomes. These findings suggest an STN topography for improving airflow for speech, in turn improving how PD patients' voices sound.

    View details for DOI 10.1093/neuros/nyaa024

    View details for PubMedID 32199026

  • DBS in major depression Deep Brain Stimulation: Techniques and Practice Kratter, I. H., Richardson, R., Karp, J. F. Thieme Medical Publishers. 2019
  • Serine 421 regulates mutant huntingtin toxicity and clearance in mice JOURNAL OF CLINICAL INVESTIGATION Kratter, I. H., Zahed, H., Lau, A., Tsvetkov, A. S., Daub, A. C., Weiberth, K. F., Gu, X., Saudou, F., Humbert, S., Yang, X., Osmand, A., Steffan, J. S., Masliah, E., Finkbeiner, S. 2016; 126 (9): 3585–97


    Huntington's disease (HD) is a progressive, adult-onset neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the N-terminal region of the protein huntingtin (HTT). There are no cures or disease-modifying therapies for HD. HTT has a highly conserved Akt phosphorylation site at serine 421, and prior work in HD models found that phosphorylation at S421 (S421-P) diminishes the toxicity of mutant HTT (mHTT) fragments in neuronal cultures. However, whether S421-P affects the toxicity of mHTT in vivo remains unknown. In this work, we used murine models to investigate the role of S421-P in HTT-induced neurodegeneration. Specifically, we mutated the human mHTT gene within a BAC to express either an aspartic acid or an alanine at position 421, mimicking tonic phosphorylation (mHTT-S421D mice) or preventing phosphorylation (mHTT-S421A mice), respectively. Mimicking HTT phosphorylation strongly ameliorated mHTT-induced behavioral dysfunction and striatal neurodegeneration, whereas neuronal dysfunction persisted when S421 phosphorylation was blocked. We found that S421 phosphorylation mitigates neurodegeneration by increasing proteasome-dependent turnover of mHTT and reducing the presence of a toxic mHTT conformer. These data indicate that S421 is a potent modifier of mHTT toxicity and offer in vivo validation for S421 as a therapeutic target in HD.

    View details for DOI 10.1172/JCI80339

    View details for Web of Science ID 000382513400036

    View details for PubMedID 27525439

    View details for PubMedCentralID PMC5004962

  • Sequence-Level Analysis of the Major European Huntington Disease Haplotype AMERICAN JOURNAL OF HUMAN GENETICS Lee, J., Kim, K., Shin, A., Chao, M. J., Abu Elneel, K., Gillis, T., Mysore, J., Kaye, J. A., Zahed, H., Kratter, I. H., Daub, A. C., Finkbeiner, S., Li, H., Roach, J. C., Goodman, N., Hood, L., Myers, R. H., MacDonald, M. E., Gusella, J. F. 2015; 97 (3): 435–44


    Huntington disease (HD) reflects the dominant consequences of a CAG-repeat expansion in HTT. Analysis of common SNP-based haplotypes has revealed that most European HD subjects have distinguishable HTT haplotypes on their normal and disease chromosomes and that ∼50% of the latter share the same major HD haplotype. We reasoned that sequence-level investigation of this founder haplotype could provide significant insights into the history of HD and valuable information for gene-targeting approaches. Consequently, we performed whole-genome sequencing of HD and control subjects from four independent families in whom the major European HD haplotype segregates with the disease. Analysis of the full-sequence-based HTT haplotype indicated that these four families share a common ancestor sufficiently distant to have permitted the accumulation of family-specific variants. Confirmation of new CAG-expansion mutations on this haplotype suggests that unlike most founders of human disease, the common ancestor of HD-affected families with the major haplotype most likely did not have HD. Further, availability of the full sequence data validated the use of SNP imputation to predict the optimal variants for capturing heterozygosity in personalized allele-specific gene-silencing approaches. As few as ten SNPs are capable of revealing heterozygosity in more than 97% of European HD subjects. Extension of allele-specific silencing strategies to the few remaining homozygous individuals is likely to be achievable through additional known SNPs and discovery of private variants by complete sequencing of HTT. These data suggest that the current development of gene-based targeting for HD could be extended to personalized allele-specific approaches in essentially all HD individuals of European ancestry.

    View details for DOI 10.1016/j.ajhg.2015.07.017

    View details for Web of Science ID 000361084700006

    View details for PubMedID 26320893

    View details for PubMedCentralID PMC4564985

  • Targeting H3K4 trimethylation in Huntington disease PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Vashishtha, M., Ng, C. W., Yildirim, F., Gipson, T. A., Kratter, I. H., Bodai, L., Song, W., Lau, A., Labadorf, A., Vogel-Ciernia, A., Troncosco, J., Ross, C. A., Bates, G. P., Krainc, D., Sadri-Vakili, G., Finkbeiner, S., Marsh, J., Housman, D. E., Fraenkel, E., Thompson, L. M. 2013; 110 (32): E3027–E3036


    Transcriptional dysregulation is an early feature of Huntington disease (HD). We observed gene-specific changes in histone H3 lysine 4 trimethylation (H3K4me3) at transcriptionally repressed promoters in R6/2 mouse and human HD brain. Genome-wide analysis showed a chromatin signature for this mark. Reducing the levels of the H3K4 demethylase SMCX/Jarid1c in primary neurons reversed down-regulation of key neuronal genes caused by mutant Huntingtin expression. Finally, reduction of SMCX/Jarid1c in primary neurons from BACHD mice or the single Jarid1 in a Drosophila HD model was protective. Therefore, targeting this epigenetic signature may be an effective strategy to ameliorate the consequences of HD.

    View details for DOI 10.1073/pnas.1311323110

    View details for Web of Science ID 000322771100015

    View details for PubMedID 23872847

    View details for PubMedCentralID PMC3740882

  • PolyQ Disease: Too Many Qs, Too Much Function? NEURON Kratter, I. H., Finkbeiner, S. 2010; 67 (6): 897–99


    The nature of the gain-of-function toxicity found in polyglutamine (polyQ) diseases has been the subject of considerable debate. In this issue of Neuron, Duvick et al. and Nedelsky et al. show that, in two of these diseases, pathology is mediated by normal protein activity.

    View details for DOI 10.1016/j.neuron.2010.09.012

    View details for Web of Science ID 000282801100001

    View details for PubMedID 20869586

    View details for PubMedCentralID PMC3989162

  • Stereoselective macrocyclization through zirconocene-mediated coupling of achiral dialkynes CHEMICAL COMMUNICATIONS Tannaci, J. F., Kratter, I. H., Rider, E. A., McBee, J. L., Miller, A. D., Tilley, T. 2009: 233–34


    1,4-Bis[trimethylsilyl(ethynyl)]naphthalene () and 1,4-bis[trimethylsilyl(ethynyl)]anthracene () undergo diastereoselective coupling with Cp2Zr(py)(Me3SiC[triple bond, length as m-dash]CSiMe3) to give trimeric macrocycles in good yield.

    View details for DOI 10.1039/b815750b

    View details for Web of Science ID 000261960400026

    View details for PubMedID 19099079