Loss-of-function mutations in the C9ORF72 mouse ortholog cause fatal autoimmune disease.
Science Translational Medicine 8(347):347ra93 (2016)
C9ORF72 mutations are found in a significant fraction of patients suffering from amyotrophic lateral sclerosis and frontotemporal dementia, yet the function of the C9ORF72 gene product remains poorly understood. We show that mice harboring loss-of-function mutations in the ortholog of C9ORF72 de...
Pigmented Lesions of the Nervous System and the Neural Crest: Lessons From Embryology.
Neurosurgery 78(1):142 (2016)
Neurosurgeons encounter a number of pigmented tumors of the central nervous system in a variety of locations, including primary central nervous system melanoma, blue nevus of the spinal cord, and melanotic schwannoma. When examined through the lens of embryology, pigmented lesions share a unifyi...
Case Records of the Massachusetts General Hospital. Case 30-2015: A 50-Year-Old Man with Cardiogenic Shock.
New England Journal of Medicine 373(13):1251 (2015)
A 50-year-old man with a history of cardiomyopathy and progressive muscle weakness was admitted with cardiogenic shock. Electroencephalography showed total suppression of cerebral activity; ventilator support was withdrawn, and he died. An autopsy was performed.
Evidence for α-synuclein prions causing multiple system atrophy in humans with parkinsonism.
PNAS 112(38):E5308 (2015)
Prions are proteins that adopt alternative conformations that become self-propagating; the PrP(Sc) prion causes the rare human disorder Creutzfeldt-Jakob disease (CJD). We report here that multiple system atrophy (MSA) is caused by a different human prion composed of the α-synuclein protein. MSA...
Propagation of prions causing synucleinopathies in cultured cells.
PNAS 112(35):E4949 (2015)
Increasingly, evidence argues that many neurodegenerative diseases, including progressive supranuclear palsy (PSP), are caused by prions, which are alternatively folded proteins undergoing self-propagation. In earlier studies, PSP prions were detected by infecting human embryonic kidney (HEK) ce...
Identification of neurotoxic cytokines by profiling Alzheimer's disease tissues and neuron culture viability screening.
Scientific reports 5:16622 (2015)
Alzheimer's disease (AD) therapeutics based on the amyloid hypothesis have shown minimal efficacy in patients, suggesting that the activity of amyloid beta (Aβ) represents only one aspect of AD pathogenesis. Since neuroinflammation is thought to play an important role in AD, we hypothesized that...
VE1 antibody immunoreactivity in normal anterior pituitary and adrenal cortex without detectable BRAF V600E mutations.
American Journal of Clinical Pathology 141(6):811 (2014)
The VE1 monoclonal antibody was developed to recognize the V600E mutation in BRAF, which is found in various tumors.
We report that the VE1 antibody stains normal anterior pituitary gland and adrenal cortex, which lack detectable BRAF V600E mutations.
Staining with the VE1 antibody was seen in t...
Glioblastoma mimicking an arteriovenous malformation.
Frontiers in Neurology 4:144 (2013)
Abnormal cerebral vasculature can be a manifestation of a vascular malformation or a neoplastic process. We report the case of a patient with angiography-negative subarachnoid hemorrhage (SAH) who re-presented 3 years later with a large intraparenchymal hemorrhage. Although imaging following the...
Cytopathology of subacute thyroiditis.
Diagnostic Cytopathology 40(5):433 (2012)
A workshop on leadership for MD/PhD students.
Medical Education Online 16 (2011)
Success in academic medicine requires scientific and clinical aptitude and the ability to lead a team effectively. Although combined MD/PhD training programs invest considerably in the former, they often do not provide structured educational opportunities in leadership, especially as applied to ...
Dpb11 activates the Mec1-Ddc2 complex.
PNAS 105(48):18730 (2008)
The Saccharomyces cerevisiae Mec1-Ddc2 checkpoint kinase complex (the ortholog to human ATR-ATRIP) is an essential regulator of genomic integrity. The S. cerevisiae BRCT repeat protein Dpb11 functions in the initiation of both DNA replication and cell cycle checkpoints. Here, we report a genetic...
The basic cleft of RPA70N binds multiple checkpoint proteins, including RAD9, to regulate ATR signaling.
Molecular and Cellular Biology 28(24):7345 (2008)
ATR kinase activation requires the recruitment of the ATR-ATRIP and RAD9-HUS1-RAD1 (9-1-1) checkpoint complexes to sites of DNA damage or replication stress. Replication protein A (RPA) bound to single-stranded DNA is at least part of the molecular recognition element that recruits these checkpo...
Activation of ATR and related PIKKs.
Cell Cycle 7(18):2809 (2008)
The DNA damage response kinase ATR is an essential regulator of genome integrity. TopBP1 functions as a general activator of ATR. We have recently shown that TopBP1 activates ATR through its regulatory subunit ATRIP and a PIKK regulatory domain (PRD) located adjacent to its kinase domain. This m...
TopBP1 activates ATR through ATRIP and a PIKK regulatory domain.
Genes & Development 22(11):1478 (2008)
The ATR (ATM and Rad3-related) kinase and its regulatory partner ATRIP (ATR-interacting protein) coordinate checkpoint responses to DNA damage and replication stress. TopBP1 functions as a general activator of ATR. However, the mechanism by which TopBP1 activates ATR is unknown. Here, we show th...
Function of a conserved checkpoint recruitment domain in ATRIP proteins.
Molecular and Cellular Biology 27(9):3367 (2007)
The ATR (ATM and Rad3-related) kinase is essential to maintain genomic integrity. ATR is recruited to DNA lesions in part through its association with ATR-interacting protein (ATRIP), which in turn interacts with the single-stranded DNA binding protein RPA (replication protein A). In this study,...