- Emergency Medicine
- Medical Education
Clinical Instructor, Emergency Medicine
Honors & Awards
SAEM/RAMS Innovative Educator Award, Society of Academic Emergency Medicine. (2021)
Chief Resident, University of California Davis, Emergency Medicine Residency Program (2020 - 2021)
Alpha Omega Alpha Honor Society Induction, University of Chicago, Pritzker School of Medicine (2013)
NIH Research Scholar, Howard Hughes Medical Institute (2010 - 2012)
MHPE Candidate, University of Illinois at Chicago, Health Professions Education
Residency: UC Davis Emergency Medicine Residency (2021) CA
Residency, UCLA Neurosurgery Residency (2013 - 2017) CA
Medical Education: Pritzker School of Medicine University of Chicago Registrar (2013) IL
Partial loss of TDP-43 function causes phenotypes of amyotrophic lateral sclerosis.
Proceedings of the National Academy of Sciences of the United States of America
2014; 111 (12): E1121-9
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disease that causes motor neuron degeneration, progressive motor dysfunction, paralysis, and death. Although multiple causes have been identified for this disease, >95% of ALS cases show aggregation of transactive response DNA binding protein (TDP-43) accompanied by its nuclear depletion. Therefore, the TDP-43 pathology may be a converging point in the pathogenesis that originates from various initial triggers. The aggregation is thought to result from TDP-43 misfolding, which could generate cellular toxicity. However, the aggregation as well as the nuclear depletion could also lead to a partial loss of TDP-43 function or TDP-43 dysfunction. To investigate the impact of TDP-43 dysfunction, we generated a transgenic mouse model for a partial loss of TDP-43 function using transgenic RNAi. These mice show ubiquitous transgene expression and TDP-43 knockdown in both the periphery and the central nervous system (CNS). Strikingly, these mice develop progressive neurodegeneration prominently in cortical layer V and spinal ventral horn, motor dysfunction, paralysis, and death. Furthermore, examination of splicing patterns of TDP-43 target genes in human ALS revealed changes consistent with TDP-43 dysfunction. These results suggest that the CNS, particularly motor neurons, possess a heightened vulnerability to TDP-43 dysfunction. Additionally, because TDP-43 knockdown predominantly occur in astrocytes in the spinal cord of these mice, our results suggest that TDP-43 dysfunction in astrocytes is an important driver for motor neuron degeneration and clinical phenotypes of ALS.
View details for DOI 10.1073/pnas.1322641111
View details for PubMedID 24616503
View details for PubMedCentralID PMC3970502
Amyotrophic lateral sclerosis-related VAPB P56S mutation differentially affects the function and survival of corticospinal and spinal motor neurons.
Human molecular genetics
2013; 22 (21): 4293-305
The substitution of Proline with Serine at residue 56 (P56S) of vesicle-associated membrane protein-associated protein B (VAPB) has been linked to an atypical autosomal dominant form of familial amyotrophic lateral sclerosis 8 (ALS8). To investigate the pathogenic mechanism of P56S VAPB in ALS, we generated transgenic (Tg) mice that heterologously express human wild-type (WT) and P56S VAPB under the control of a pan-neuronal promoter Thy1.2. While WT VAPB Tg mice did not exhibit any overt motor behavioral phenotypes, P56S VAPB Tg mice developed progressive hyperactivities and other motor abnormalities. VAPB protein was accumulated as large punctate in the soma and proximal dendrites of both corticospinal motor neurons (CSMNs) and spinal motor neurons (SMNs) in P56S VAPB Tg mice. Concomitantly, a significant increase of endoplasmic reticulum stress and unfolded protein response and the resulting up-regulation of pro-apoptotic factor CCAAT/enhancer-binding protein homologous protein expression were observed in the CSMNs and SMNs of P56S VAPB Tg mice. However, only a progressive loss of CSMNs but not SMNs was found in P56S VAPB Tg mice. In SMNs, P56S VAPB promoted a rather selective translocation of VAPB protein onto the postsynaptic site of C-boutons that altered the morphology of C-boutons and impaired the spontaneous rhythmic discharges of SMNs. Therefore, these findings provide new pathophysiological mechanisms of P56S VAPB that differentially affect the function and survival of CSMNs and SMNs in ALS8.
View details for DOI 10.1093/hmg/ddt279
View details for PubMedID 23771029
View details for PubMedCentralID PMC3792689
A novel scoring system for assessing Chiari malformation type I treatment outcomes.
2012; 70 (3): 656-64; discussion 664-5
Outcome assessment for the management of Chiari malformation type 1 is difficult because of the lack of a reliable and specific surgical outcome assessment scale. Such a scale could reliably correlate postoperative outcomes with preoperative symptoms.We developed a novel scoring system and applied it retrospectively to 146 patients treated at our institution in order to create and verify a simple and quantifiable assessment of Chiari outcomes.The Chicago Chiari Outcome Scale (CCOS) uses 4 postoperative outcome categories (pain, nonpain symptoms, functionality, and complications) graded 1 to 4 for a total possible score of 16. As a comparison with current Chiari outcome methodology, each patient was also placed into a gestalt outcome group of "improved," "unchanged," or "worse" (I/U/W). Patients were stratified by CCOS scores and by I/U/W group.Stratifying patients by total CCOS scores showed that patients who achieved CCOS scores between 13 and 16 were predominantly in the I/U/W improved group (n = 101, 69%); scores between 9 and 12 were predominantly I/U/W unchanged (n = 39, 27%), and scores between 4 and 8 were I/U/W worse (n = 6, 4%). Symptom subscore results provided insight into the specifics of the overall outcome in addition to the more quantitative nature of the 16-point scale.We describe a CCOS that assigns higher scores to patients judged improved by gestalt I/U/W ratings and lower scores to those who were unchanged or worse while defining outcome in 4 specific subcategories. As such, this CCOS should allow for a more unified and quantifiable outcome assessment after Chiari surgery.
View details for DOI 10.1227/NEU.0b013e31823200a6
View details for PubMedID 21849925
View details for PubMedCentralID PMC6718293
Positive and negative predictors for good outcome after decompressive surgery for Chiari malformation type 1 as scored on the Chicago Chiari Outcome Scale.
2012; 34 (7): 694-700
Posterior fossa decompression (PFD) is commonly applied as treatment for Chiari malformation type 1 (CM1), an entity which is associated with a variety of presenting symptoms but little data correlating symptoms to surgical outcome. We applied the Chicago Chiari Outcome Scale (CCOS), a novel 16-point tool for evaluating outcome, to a consecutive series of CM1 patients to identify specific factors or symptoms that predispose to a better or worse surgical outcome.A series of 167 CM1 patients who underwent initial PFD at our institution (consisting of suboccipital craniectomy, C1 laminectomy, subarachnoid exploration, and expansile autologous pericranial duraplasty) were reviewed. Pre-operative signs, symptoms, and characteristics were recorded, and odds ratios were calculated to identify significant pre-operative factors corresponding to a better or worse outcome on the CCOS.Sensory deficits and peripheral neuropathy correlated with a lower score on the CCOS. Younger age at the time of surgery and, strikingly, presence of syringomyelia both correlated with a higher CCOS score.Our results identify specific presenting factors that correlated with a better or worse outcome after CM1 decompression. These data also demonstrate that CCOS scoring allows for a rigorous comparison of outcome in different patient populations and between variable operative techniques. Application of CCOS scoring to a larger patient population undergoing a variety of operative CM1 treatments should allow for better-informed decisions regarding patient selection and treatment options for CM1.
View details for DOI 10.1179/1743132812Y.0000000066
View details for PubMedID 22781921
View details for PubMedCentralID PMC6718292
α-synuclein, LRRK2 and their interplay in Parkinson's disease.
2012; 7 (2): 145-153
Of the various genetic factors contributing to the pathogenesis of Parkinson's disease (PD), only mutations in α-synuclein (α-syn) and LRRK2 genes cause clinical and neuropathological phenotypes closely resembling the sporadic cases. Therefore, studying the pathophysiological functions of these two PD-related genes is particularly informative in understanding the underlying molecular pathogenic mechanism of the disease. PD-related missense and multiplication mutations in α-syn may cause both early- and late-onset PD, whereas various PD-related LRRK2 missense mutations may contribute to the more common late-onset PD. While intensive studies have been carried out to elucidate the pathogenic properties of PD-related mutant α-syn and LRRK2, our knowledge of their normal functions and their potential genetic interplay remains rudimental. In this review, we summarize the progress made regarding the pathophysiological functions of α-syn, LRRK2 and their interaction in PD, based on the available literature and our unpublished observations.
View details for DOI 10.2217/fnl.12.2
View details for PubMedID 22563296
View details for PubMedCentralID PMC3343692