Dementia
SELECTED PUBLICATIONS
STAT3 inhibitor mitigates cerebral amyloid angiopathy and parenchymal amyloid plaques while improving cognitive functions and brain networks
Acta Neuropathologica Communications vol 9,
Article number: 193 (2021)
Previous reports indicate a potential role for signal transducer and activator of transcription 3 (STAT3) in amyloid-β (Aβ) processing and neuritic plaque pathogenesis. In the present study, the impact of STAT3 inhibition on cognition, cerebrovascular function, amyloid pathology, oxidative stress, and neuroinflammation was studied using in vitro and in vivo models of Alzheimer’s disease (AD)-related pathology. Our results demonstrated functional improvements associated with a reduction in neuritic plaques, cerebral amyloid angiopathy (CAA), oxidative stress, and neuroinflammation. Reduction in amyloid precursor protein (APP) processing and attenuation of oxidative modification of lipoprotein receptor related protein-1 (LRP-1) were identified as potential underlying mechanisms. These results demonstrate the broad impact of STAT3 on cognitive functions, parenchymal and vascular amyloid pathology and highlight the therapeutic potential of STAT3 specific inhibition for treatment of AD and CAA.
For details, click here.
APOE immunotherapy reduces cerebral amyloid angiopathy and amyloid plaques while improving cerebrovascular function
The ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer’s disease (AD) and greatly influences the development of amyloid-β (Aβ) pathology. Our current study investigated the potential therapeutic effects of the anti-human APOE antibody HAE-4, which selectively recognizes human APOE that is co-deposited with Aβ in cerebral amyloid angiopathy (CAA) and parenchymal amyloid pathology. In chronically treated 5XE4 mice, HAE-4 reduced Aβ deposition including CAA compared to a control antibody, whereas the anti–Aβ antibody had no effect on CAA. Furthermore, the anti–Aβ antibody exacerbated microhemorrhage severity, which highly correlated with reactive astrocytes surrounding CAA. In contrast, HAE-4 did not stimulate microhemorrhages and instead rescued CAA-induced cerebrovascular dysfunction in leptomeningeal arteries in vivo. HAE-4 not only reduced amyloid but also dampened reactive microglial, astrocytic, and proinflammatory-associated genes in the cortex. These results suggest that targeting APOE in the core of both CAA and plaques could ameliorate amyloid pathology while protecting cerebrovascular integrity and function.
For details, click here.
Passive immunotherapy targeting amyloid-β reduces cerebral amyloid angiopathy and improves vascular reactivity
Brain. 2016 Feb;139(Pt 2):563-77.
Chronic administration of the anti-Aβ40 specific antibody, ponezumab, reduced Aβ accumulation both in leptomeningeal and brain vessels in aged Tg2576 mice. Acute administration of ponezumab triggered a significant and transient increase in interstitial fluid Aβ40 levels in aged Tg2576 mice. A beneficial effect on vascular reactivity following acute administration of ponezumab was also noted, even in vessels where there was severe CAA. These data favor a mechanism that involves rapid removal and/or neutralization of Aβ species that may otherwise be detrimental to normal vessel function.
For details, click here.
Heparan sulfate proteoglycans (HSPG) mediate Aβ-induced oxidative stress and hypercontractility in cultured vascular smooth muscle cells (VSMC)
Mol Neurodegener. 2016 Jan;11:9
We demonstrated that pharmacological depletion of HSPG in cultured VSMC mitigates Aβ40- and Aβ42-induced oxidative stress. We also found that Aβ40 (but not Aβ42) causes a hypercontractile phenotype in cultured VSMC that likely results from a HSPG-mediated augmentation in intracellular Ca(2+) activity. Taken together, our data indicate that HSPG are critical mediators of Aβ-induced oxidative stress and Aβ40-induced VSMC dysfunction, and suggests HSPG may play a critical core in CAA-induced cerebrovascular dysfunction and CAA pathogenesis.
For details, click here.
Contribution of reactive oxygen species to cerebral amyloid angiopathy, vasomotor dysfunction, and microhemorrhage in aged Tg2576 mice
Proc Natl Acad Sci U S A. 2015 Feb;112(8):E881-90
We showed that the NADPH oxidase inhibitor, apocynin, and the free radical scavenger, tempol, reduce oxidative stress and improve vessel reactivity in aged Tg2576 mice; the improved cerebrovascular function is due to reduction in CAA formation and a decrease in CAA-induced vasomotor impairment; and antioxidant therapies attenuate CAA-related microhemorrhage. These results indicate oxidative stress is a key contributor to CAA formation, CAA-induced vessel dysfunction, and CAA-related microhemorrhage, and suggest that NADPH oxidase-derived oxidative stress is a promising therapeutic target for patients with CAA and Alzheimer's disease.
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Cerebral amyloid angiopathy (CAA) increases susceptibility to infarction after focal cerebral ischemia in Tg2576 mice
Stroke. 2014 Oct;45(10):3064-9.
We demonstrated that aged Tg2576 mice have more severe cerebrovascular dysfunction that is CAA dependent, have greater cerebral blood flow compromise during and immediately after middle cerebral artery occlusion, and develop larger infarctions after middle cerebral artery occlusion. These data indicate CAA induces a more severe form of cerebrovascular dysfunction than soluble Aβ alone, leading to intra- and postischemic cerebral blood flow deficits that ultimately exacerbate cerebral infarction.
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Resorufin analogs preferentially bind cerebrovascular amyloid: potential use as imaging ligands for cerebral amyloid angiopathy
Mol Neurodegener. 2011 Dec;6:86
We demonstrated that the phenoxazine derivative, resorufin, preferentially binds CAA (arrowheads) over neuritic plaques (arrows) in aged Tg2576 mice. We also found that resorufin staining was predominantly noted in amyloid-laden vessels in postmortem Alzheimer's brain tissues, and that resorufin selectively visualizes CAA in live Tg2576 mice when topically administered. Resorufin analogs are the fist class of amyloid dye that discriminate between cerebrovascular and neuritic forms of amyloid. This binding selectivity suggests resorufin analogs have great potential as a CAA-specific amyloid tracer that could permit non-invasive detection and quantification of CAA in live patients.
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Cerebrovascular dysfunction in amyloid precursor protein transgenic mice: contribution of soluble and insoluble amyloid-beta peptide, partial restoration via gamma-secretase inhibition
J Neurosci. 2008 Dec;28(50):13542-50
We showed that a strong correlation between CAA severity and vessel reactivity exists in Tg2576 mice; a surprisingly small amount of CAA produces marked reduction or complete loss of vessel function; CAA-induced vasomotor impairment results from dysfunction rather than loss or disruption of vascular smooth muscle cells; and acute depletion of Aβ improves vessel function in young and to a lesser degree aged Tg2576 mice. These results suggest soluble and insoluble Aβ causes vasomotor impairment, that mechanisms other than Aβ-induced alteration in vessel integrity are responsible, and that anti-Aβ therapy may have beneficial effects on vascular as well as parenchymal amyloid.
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Aneurysmal Subarachnoid Hemorrhage (SAH)
SELECTED PUBLICATIONS
Inhalational Versus Intravenous
Anesthetic Conditioning for Subarachnoid
Hemorrhage–Induced Delayed Cerebral Ischemia
Stroke. 2022;53:904–912. DOI: 10.1161/STROKEAHA.121.035075
BACKGROUND: Inhalational anesthetics were associated with reduced incidence of angiographic vasospasm and delayedcerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (SAH). Whether intravenous anesthetics
provide similar level of protection is not known.
METHODS: Anesthetic data were collected retrospectively for patients with SAH who received general anesthesia for aneurysmrepair between January 1, 2014 and May 31, 2018, at 2 academic centers in the United States (one employing primarily
inhalational and the other primarily intravenous anesthesia with propofol). We compared the outcomes of angiographic
vasospasm, DCI, and neurological outcome (measured by disposition at hospital discharge), between the 2 sites, adjusting
for potential confounders.
RESULTS: We compared 179 patients with SAH receiving inhalational anesthetics at one institution to 206 patients withSAH receiving intravenous anesthetics at the second institution. The rates of angiographic vasospasm between inhalational
versus intravenous anesthetic groups were 32% versus 52% (odds ratio, 0.49 [CI, 0.32–0.75]; P=0.001) and DCI were21% versus 40% (odds ratio, 0.47 [CI, 0.29–0.74]; P=0.001), adjusting for imbalances between sites/groups, Hunt-Hessand Fisher grades, type of aneurysm treatment, and American Society of Anesthesiology status. No impact of anesthetics
on neurological outcome at time of discharge was noted with rates of good discharge outcome between inhalational versus
intravenous anesthetic groups at (78% versus 72%, P=0.23).CONCLUSIONS: Our data suggest that those who received inhalational versus intravenous anesthetic for ruptured aneurysm repairhad significant protection against SAH-induced angiographic vasospasm and DCI. Although we cannot fully disentangle site-
specific versus anesthetic effects in this comparative study, these results, when coupled with preclinical data demonstrating
a similar protective effect of inhalational anesthetics on vasospasm and DCI, suggest that inhalational anesthetics may be
preferable for patients with SAH undergoing aneurysm repair. Additional investigations examining the effect of inhalational
anesthetics on other SAH outcomes such as early brain injury and long-term neurological outcomes are warranted.
For details, click here.
SIRT1 mediates hypoxic postconditioning- and resveratrol-induced protection against functional connectivity deficits after subarachnoid hemorrhage
Journal of Cerebral Blood Flow & Metabolism. 2022;42(7):1210-1223. doi:10.1177/0271678X221079902
Functional connectivity (FC) is a sensitive metric that provides a readout of whole cortex coordinate neural activity in a mouse model. We examine the impact of experimental SAH modeled through endovascular perforation, and the effectiveness of subsequent treatment on FC, through three key questions: 1) Does the endovascular perforation model of SAH induce deficits in FC; 2) Does exposure to hypoxic conditioning provide protection against these FC deficits and, if so, is this neurovascular protection SIRT1-mediated; and 3) does treatment with the SIRT1 activator resveratrol alone provide protection against these FC deficits? Cranial windows were adhered on skull-intact mice that were then subjected to either sham or SAH surgery and either left untreated or treated with hypoxic post-conditioning (with or without EX527) or resveratrol for 3 days. Mice were imaged 3 days post-SAH/sham surgery, temporally aligned with the onset of major SAH sequela in mice. Here we show that the endovascular perforation model of SAH induces global and network-specific deficits in FC by day 3, corresponding with the time frame of DCI in mice. Hypoxic conditioning provides SIRT1-mediated protection against these network-specific FC deficits post-SAH, as does treatment with resveratrol. Conditioning-based strategies provide multifaceted neurovascular protection in experimental SAH.
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SIRT1 mediates hypoxic preconditioning induced attenuation of neurovascular dysfunction following subarachnoid hemorrhage
Exp Neurol. 2020 Dec;334:113484.
We used the SIRT1-specific inhibitor, EX527, and the SIRT1 activator, Resveratrol, to show that hypoxia-induced augmentation of SIRT1 is a critical molecular mediator of the robust neurovascular protection afforded by hypoxic preconditioning in experimental SAH. These results indicate SIRT1 activation is a promising, novel, pleiotropic therapeutic strategy to combat Delayed Cerebral Ischemia after SAH.
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Role of eNOS in Isoflurane Conditioning-Induced Neurovascular Protection in Subarachnoid Hemorrhage
J Am Heart Assoc 2020. Oct 2019(20):e017477.
We used the pan nitric oxide synthase inhibitor, L-NAME, along with genetically modified mice constitutively lacking eNOS to show that the robust protection afforded by isoflurane conditioning against SAH-induced delayed cerebral ischemia is critically mediated via isoflurane-induced augmentation in eNOS.
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Microvascular platelet aggregation and thrombosis after subarachnoid hemorrhage: A review and synthesis
JCBFM. 2020 Aug; 40(8):1565-1575
The focus of this review is to provide an overview of experimental animal model studies and human autopsy studies that explore the temporal- spatial characterization and mechanism of microvascular platelet aggregation and thrombosis following subarachnoid hemorrhage (SAH), as well as to critically assess experimental studies and clinical trials highlighting preventative therapeutic options against this highly morbid pathophysiological process.
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Minocycline protects against delayed cerebral ischemia after subarachnoid hemorrhage via MMP‐9 inhibition
Ann Clin Transl Neurol. 2017 Oct;4(12):865-876
We demonstrated that MMP-9 expression and activity are increased after subarachnoid hemorrhage in mice. We also showed that genetic (MMP-9 knockout) and pharmacological (minocycline) inhibition of MMP-9 decreases vasospasm and neurobehavioral deficits in mice, and that minocycline administration to MMP-9 knockout mice does not yield additional protection. We also showed that minocycline reduces vasospasm in rabbits. These data indicate MMP-9 is a key player in the pathogenesis of subarachnoid hemorrhage-induced delayed cerebral ischemia, and that minocycline has promise as a novel MMP-9 directed therapy for subarachnoid hemorrhage patients.
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A novel fluorescent imaging technique for assessment of cerebral vasospasm after experimental subarachnoid hemorrhage
Sci Rep. 2017 Aug;7(1):9126
We applied ROX SE fluorescent imaging to our mouse model of subarachnoid hemorrhage and found that this novel imaging technique is qualitatively and quantitatively superior to India ink-gelatin casting for the assessment of cerebral vasospasm, while also permitting outstanding immunohistochemical examination of non-vasospasm components of secondary brain injury.
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A Phase I proof-of-concept and safety trial of sildenafil to treat cerebral vasospasm following subarachnoid hemorrhage
J Neurosurg. 2016 Feb;124(2):318-27
Subarachnoid hemorrhage patients with angiographically confirmed vasospasm were treated with intravenous silenafil and monitored for safety and efficacy. Of the 12 treated patients, 8 (67%) had a positive angiographic response, 3 (60%) in the low-dose group and 5 (71%) in the high-dose group. The largest degree of vessel dilation was an average of 0.8 mm (range 0-2.1 mm). This corresponded to an average percentage increase in vessel diameter of 62% (range 0%-200%). Results from this Phase I clinical trial showed sildenafil is safe and well tolerated in the setting of subarachnoid hemorrhage and suggest a positive impact on vasospasm.
For details, click here.
HIF-1α Mediates Isoflurane-Induced Vascular Protection in Subarachnoid Hemorrhage
Ann Clin Transl Neurol 2015. Apr;2(4):325-37
Isoflurane postconditioning reduced cerebral vasospasm, microvessel thrombosis, microvascular dysfunction, and neurological deficits in wild-type mice. Isoflurane-induced protection against subarachnoid hemorrhage-induced delayed cerebral ischemia was attenuated in 2ME2-treated wild-type mice and endothelial cell-specific HIF-1α-null mice. These results implicate cerebral vessels as a key target for the brain protection afforded by isoflurane postconditioning, and HIF-1α as a critical mediator of this vascular protection. They also identify isoflurane postconditioning as a promising novel therapeutic for subarachnoid hemorrhage.
For details, click here.
eNOS Mediates Endogenous Protection Against Subarachnoid Hemorrhage-induced Cerebral Vasospasm
Stroke 2011. Mar;42(3):776-82
Hypoxic preconditioning (PC) nearly completely prevented subarachnoid hemorrhage-induced reduction in nitric oxidate availability, vasospasm and neurological deficits. This protection was lost in wild-type mice treated with the nitric oxide synthase inhibitor, L-NAME, and in eNOS-null mice. These data indicate endogenous protective mechanisms against vasospasm exist, are powerful, can be induced by PC, and are critically dependent on eNOS-derived nitric oxide. They also suggest conditioning-based therapy is a promising new strategy to reduce vasospasm and delayed cerebral ischemia after subarachnoid hemorrhage.
For details, click here.
Amyloid-β Dynamics Correlate with Neurological Status in the Injured Human Brain
Science. 2008 Aug;321(5893):1221-4
We used intracerebral microdialysis to obtain serial brain interstitial fluid samples in patients undergoing invasive intracranial monitoring after acute brain injury. We found a strong positive correlation between changes in brain interstitial fluid Aβ concentrations and neurological status. We also found that brain interstitial fluid Aβ concentrations were lower when other cerebral physiological and metabolic abnormalities reflected depressed neuronal function. Such dynamics fit well with the hypothesis that neuronal activity regulates extracellular Aβ concentrations.
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Consortium for dAVF Outcome Research (CONDOR)
SELECTED PUBLICATIONS
Introduction. The Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR)
J Neurosurg. 2021 Sep 10:1-2. doi: 10.3171/2021.1.JNS2174
We established an international multicenter consortium referred to as the Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR).
In this issue of the Journal of Neurosurgery, we provide an introductory article focused on the rationale and principles for establishment of CONDOR and initial characterization of its 1077-patient cohort. This article is followed by four complementary CONDOR studies examining various aspects of dAVF presentation, management, and outcome. Several additional research projects leveraging this large and unique dAVF patient cohort are also currently underway. Based on our initial results, we are very optimistic that efforts from this multicenter dAVF consortium will bring better understanding and novel insights into this rare cerebrovascular disorder that will ultimately lead to better clinical decision-making and improved patient outcome.
For details, click here.
Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR): rationale, design, and initial characterization of patient cohort
J Neurosurg. 2021 Sep 10;136(4):951-961. doi: 10.3171/2021.1.JNS202790
CONDOR comprises 14 centers in the United States, the United Kingdom, the Netherlands, and Japan that have pooled their data from 1077 dAVF patients seen between 1990 and 2017. The cohort includes 359 patients (33%) with Borden type I dAVFs, 175 (16%) with Borden type II fistulas, and 529 (49%) with Borden type III fistulas. Overall, 852 patients (79%) presented with fistula-related symptoms: 427 (40%) presented with nonaggressive symptoms such as tinnitus or orbital phenomena, 258 (24%) presented with intracranial hemorrhage, and 167 (16%) presented with nonhemorrhagic neurological deficits. A smaller proportion (224 patients, 21%), whose dAVFs were discovered incidentally, were asymptomatic. Many patients (85%, 911/1077) underwent treatment via endovascular embolization (55%, 587/1077), surgery (10%, 103/1077), radiosurgery (3%, 36/1077), or multimodal therapy (17%, 184/1077). The overall angiographic cure rate was 83% (758/911 treated), and treatment-related permanent neurological morbidity was 2% (27/1467 total procedures). The median time from diagnosis to follow-up was 380 days (IQR 120–1038.5 days). CONCLUSIONS With more than 1000 patients, the CONDOR registry represents the largest registry of cranial dAVF patient data in the world. These unique, well-annotated data will enable multiple future analyses to be performed to better understand dAVFs and their management.
For details, click here.
Outcome Following Hemorrhage From Cranial Dural Arteriovenous Fistulae
Analysis of the Multicenter International CONDOR RegistryStroke Volume 52, Issue 10, October 2021; Pages e610-e613
The CONDOR dataset yielded 262 patients with incident hemorrhage, with median follow-up of 1.4 years. Poor outcome was observed in 17.0% (95% CI, 12.3%–21.7%) at follow-up, including a 3.6% (95% CI, 1.3%–6.0%) mortality. Age and anticoagulant use were associated with poor outcome on multivariable analysis (odds ratio, 1.04, odds ratio, 5.1 respectively). Subtype of hemorrhage and venous shunting pattern of the lesion did not affect outcome significantly.
Within the CONDOR registry, dural arteriovenous fistula–related hemorrhage was associated with a relatively lower morbidity and mortality than published outcomes from other arterialized cerebrovascular lesions but still at clinically consequential rates.
For details, click here.
SELECT EXPERIMENTAL TECHNIQUES
We use a complementary set of molecular, cellular, genetic, and neurobehavioral approaches for our studies
Mouse models of amyloidosis
Aged Tg2576, PSAPP, and 5xFAD:APOE4 transgenic mice are used to study CAA (arrows) and neuritic plaques (arrowheads) that are imaged with congo red derivative dyes like X34.
Mouse model of subarachnoid hemorrhage
Endovascular perforation of the left internal carotid artery bifurcation (arrow) produces experimental subarachnoid hemorrhage in mice and rats.
Cerebral Vasospasm
Subarachnoid hemorrhage-induce cerebral vasospasm is quantified via India ink-gelatin casting (circles) or ROX SE fluorescent imaging.
Cerebrovascular Function
Pial arteriole vasoreactivity to hypercapnia and topical vasoactive agents is assessed via open cranial window technique in live mice.
Functional Connectivity by Optical Imaging
Diffuse optical tomography (DOT) is used to examine Functional Connectivity of brain networks after acute and chronic brain injury
Neurobehavior
Complementary set of neurobehavioral tests are utilized including Novel Object Recognition, Novel Object Location, Y-maze, Burrowing Behavior, and Morris Water Maze.
Smooth Muscle Cell Contractility
Contractility of cultured human-derived vascular smooth muscle cells is assessed via area measurements of cells (inset) following exposure to KCl and/or Abeta.
THE PRINCIPAL INVESTIGATOR
Gregory J. Zipfel, MD
Dr. Zipfel grew up in Peoria, IL, the son of two teachers. He attended college at the University of Illinois and graduated with honors from Northwestern University Medical School. After completing residency and fellowship at the University of Florida and the University of Miami, he returned to the Midwest in 2004 to begin his career as a neurosurgeon-scientist. Currently, Dr. Zipfel serves as Professor and Chair of Neurosurgery at Washington University and Neurosurgeon-in-Chief at Barnes-Jewish Hospital. He is a passionate clinician, scientist, educator, and mentor. He particularly enjoys the opportunity to care for patients with cerebrovascular disease while also performing fundamental research with the goal of translating findings back to the clinic to improve patient outcomes in the future.
LAB MEMBERS
We are a collaborative and diverse group of scientists driven to making fundamental discoveries in the lab and rapidly translating these insights to the clinic.
Gregory J. Zipfel, MD
Principal Investigator
Dr. Zipfel's lab has been continuously funded by the NIH since 2005 and currently includes two active R01's. He is a passionate mentor with a long track record of successful mentees -- a group that includes 5 neurosurgical, 1 neurology, and 1 anesthesiology faculty; 8 post-doctoral fellows; 13 medical students; and 11 undergraduates.
Deepti Diwan, PhD
Research Instructor
Dr. Diwan received her Ph.D. in genome profiling from Saitama University in Saitama City, Japan. She joined the Zipfel lab in 2017. She focuses her research on deciphering the molecular mechanisms underlying hypoxic post-conditioning-induced neurovascular protection in subarachnoid hemorrhage.
Jogender Mehla, PhD
Research Instructor
Dr. Mehla completed his PhD at All India Institute of Medical Sciences and a Post-Doctoral Fellowship in the labs of Drs. Robert McDonald and Majid Mohajerani at the Canadian Centre for Behavioural Neuroscience, University of Lethbridge. Dr. Mehla joined the Zipfel lab in 2019, and his research focuses on determining the role and elucidating the mechanisms of vascular oxidative stress and cerebral amyloid angiopathy in Alzheimer's disease.
Anja Srienc, MD, PhD
Resident, Neurosurgery
Dr. Srienc trained at the University of Minnesota for medical school and graduate school. She currently is a neurosurgery resident at Washington University in St. Louis. She focuses her research on elucidating the mechanisms underlying subarachnoid hemorrhage-induced cortical spreading depression and functional connectivity deficits.
Umeshkumar Athiraman, MD
Assistant Professor, Anesthesiology
Dr. Athiraman was recruited to the Anesthesiology Department at Washington University in St. Louis in 2015 and joined the Zipfel lab soon thereafter. He directs clinical anesthesia for neurosurgery and is the Program Director for the Neuroanesthesia fellowship. His research focuses on applying anesthetic conditioning to subarachnoid hemorrhage -- as a therapeutic and as a means for discovering new druggable molecular targets.
Ananth K. Vellimana, MD
Assistant Professor, Neurosurgery
Dr. Vellimana trained at All India Institute of Medical Sciences for medical school, completed a post-doctorate in the Zipfel lab, completed his neurosurgery residency and neuroendovascular fellowship at Washington University in St. Louis, and his cerebrovascular fellowship at the University of Washington. He is now an Assistant Professor of Neurosurgery. He focuses his research on elucidating the mechanisms underlying subarachnoid hemorrhage-induced delayed cerebral ischemia and hypoxic conditioning-induced brain protection in subarachnoid hemorrhage.
Jimmy Nelson, PhD
Staff Scientist
Jimmy is a former research technician in the Zipfel lab who recently completed his PhD at Baylor University. Jimmy returned as a staff scientist in the Zipfel lab in 2019. He has years of experience with a variety of experimental techniques, with special expertise in developing and advancing animal models of neurological disease.
Ernesto Gonzalez
Research Technician
Ernie is a master experimental animal surgeon who is the lead surgeon for the In Vivo Animal Surgery Core of Washington University's Hope Center. He has been a member of the Zipfel lab since 2006.
Ahmed E. Hussein, MD
PostDoc Fellow
Member of the Zipfel lab since August 2022.
Students
Our students are involved in cutting-edge Neuroscience research and contribute to the advancement of biomedical knowledge. Students are prepared for their future goals through science writing, performing many lab procedures as well as learning animal handling and microsurgical skills.
Alan Chen
Undergrad
Alan is senior at WashU dual-majoring in Neuroscience and Healthcare Management intending on pursuing medical school after graduation. He joined the lab in December 2019 and has spent summer 2020 on BIOSURF and summer 2021 in the lab. He focuses his research on elucidating causal mechanisms of oxidative stress on cerebral amyloid angiopathy and Alzheimer’s Disease in aggressive amyloidosis mouse models as well as human tissue from Alzheimer’s patients.
Kevin Oloomi
Undergrad
Kevin is currently a third-year student at WashU majoring in Biochemistry and minoring in Computer Science. He intends to pursue medical school upon graduation. He joined Dr. Zipfel's lab in Fall of 2020 and spent summer on the BioSURF scholarship in the lab.
His work primarily focuses on uncovering the biochemical pathways surrounding NAMPT activation in mice models suffering Subarachnoid Hemorrhage and oxidative stress.
Uday Vissa
Undergrad
Uday is a Senior at John Burroughs School, intends to study neuroscience in college. He Joined the lab in June 2022.
Aminah Mostafa
Undergrad
Aminah is currently a junior at WashU studying Biology and Psychology with the intention to pursue a career in medicine following her graduation. She joined the Zipfel Lab in June 2021 and has spent time studying under both Dr. Diwan and Dr. Mehla. Her current research focuses on the mechanistic links between cerebral amyloid angiopathy and Alzheimer’s disease.
Molly Dillon
Undergrad
Molly is a sophomore at WashU majoring in Biology on the Neuroscience Track with a minor in Global Health and the Environment. Molly's goal is to pursue medical school after graduation.
She joined the Zipfel Lab in August 2022 and has been an integral part of the research team focusing on Alzheimer’s Disease since then. Through her work with Dr. Mehla, Molly has learned about the pathophysiology of Dementia as well as how to perform advanced lab techniques.
Erin Walker
Undergrad
Member of the Zipfel lab since August 2022.
SOCIAL EVENTS
Celebration Lunch for recieving a new NIH R01 Grant! Congratulations Team Zipfel!
Isabella, Dr. Zipfel, Anja, Jimmy, Prakash, Ahmed, Ernie, Alan, and Bao (clockwise from bottom left)
Celebrating arrival of senior scientist, Jimmy Nelson, PhD. Welcome back Jimmy!
Jogender, Deepti, Matt, Jane, Umesh, Greg, Ernie, Jimmy, Keshav, and Meizi (clockwise from bottom left)
Alumni
We are extremely proud of all past members of the Zipfel lab
Associate Professor of Neurology, Washington University School of Medicine in Saint Louis
Lab years: 2010-2015
Position: Instructor
Assistant Professor, Neurosurgery
Loyola University
Lab years: 2012-2014
Position: Post-doctorate
Department Chair, Neurosurgery
University of Mississippi
Lab years: 2012-2014
Position: Post-doctorate
Associate Professor
Associate Program Director of the Residency Program,University of Texas-Houston
Lab years: 2008-2009
Position:Post-doctorate
Professor, Neurosurgery
Catholic University,
South Korea
Lab years: 2008-2009
Position: Post-doctorate
Meng-liang Zhou
Associate Professor, Neurosurgery
Nanjing University, China
Lab years: 2008-2010
Position: Post-doctorate
Bhuvic Patel
Van Wagenen Fellow in Dr. Felix Sahm's Lab.
Chief Resident, Neurosurgery
Washington University in St. Louis (2021-2022)
Lab years: 2012-2014
Position: Medical Student
Jacob Greenberg
Spine Fellow at the Cleveland Clinic.
Chief Resident, Neurosurgery
Washington University in St. Louis (2021-2022)
Lab years: 2010-2011
Position: Medical Student
Resident PGY-5, Neurosurgery
Washington University in St. Louis
Lab years: 2016-2017
Position:Medical Student
Neurosurgery Resident PGY-4,
Johns Hopkins University
Lab years: 2010-2013
Position: Undergraduate
Resident PGY-3, Internal Medicine,
Brigham and Women's Hospital
Lab years: 2017-2018
Position:Medical Student
Fellow, Ophthalmology
Washington University in St. Louis
Lab years: 2015-2016
Position: Medical Student
Resident PGY-4, Neurology,
Northwestern University, Chicago, IL
Lab years: 2012-2014
Position: Undergraduate
Resident PGY-2,Obstetrics/gynecologyMain Line HealthLab years: 2012-2016
Position: Undergraduate
Resident PGY-3, Pediatrics,
University of Chicago, Chicago, IL
Lab years: 2010-2013
Position: Undergraduate
Resident PGY-3, Vascular Surgery
Washington University in St. Louis
Lab year: 2017
Position:Medical Student
Matt Mollman
Physician, Emergency Medicine
Austin, TX
Lab years: 2013-2014
Position: Medical Student
Andrew Johnson
Medical Science Liaison,
Mallinckrodt Pharmaceuticals
Lab years: 2012-2014
Position: Post-doctorate
Ridhima Guniganti
Resident, Neurosurgery
Washington University in St. Louis
Lab years: 2016-2017
Position: Medical Student
David Kim
Fellow, Interventional Pain,
University of Kansas
Lab years: 2010-2011
Position: Medical Student
Eric Milner
Instructor,
Arizona State University
Lab years: 2006-2014
Position: Graduate Student
Molly Lawrence
Medical Student,
Northwestern University
Lab years: 2015-2018
Position: Undergraduate
Emily Lin
Medical Student,
Medical College of Wisconsin
Lab years: 2012-2015
Position: Undergraduate
James Baek
MSTP Student,
Indiana University
Lab years: 2012-2014
Position: Undergraduate
Yan Wang
Resident, Neurology
Washington University in St. Louis
Lab years: 2008
Position: Undergraduate
Min Yoo
Resident, PM&R
UC-Irvine
Lab years: 2007-2010
Position: Undergraduate
Keshav Jayaraman
Medical Student, Washington University in St. Louis
Lab years: 2018-2022
Position: Medical Student
News
Congratulations to Dr. Zipfel on the Drake Lectureship and for Phenomenal guidance on how to approach the stages of one's career arc!
October, 2022
Jeffrey Fort’s gift for the Department of Neurosurgery will help Gregory Zipfel, MD, and Joshua Osbun, MD, investigate ways to improve outcomes for patients with neurological conditions, including blood vessel malformations, aneurysm, and stroke
August 03, 2020
Professorship honors former neurosurgery head
December 11, 2019
“It is truly an honor to succeed my mentor and close friend as the new head of neurosurgery,” Zipfel said. “Dr. Dacey has built a world-class department over a 30-year career here at Washington University, and I see a tremendous opportunity to build upon this extraordinary foundation. I look forward to partnering with so many outstanding colleagues from the School of Medicine, Siteman Cancer Center, Hope Center, Barnes-Jewish Hospital, St. Louis Children’s Hospital and BJC, to usher in a new era of academic accomplishment, leading-edge clinical care and first-rate training in neurosurgery. Through these partnerships, I am confident that we will reach our overarching goal to make a difference in patients’ lives today, while also advancing our field so we can make an even greater difference in patients’ lives tomorrow.”
April 25, 2019
Medical student, Vivian Lee, receives the Carolyn L. Kuckein Student Research Fellowship Award from the Alpha Omega Alpha National Honor Medical Society to support her research in the Zipfel lab
August 7, 2018
St. Louis Magazine highlights the care of a young woman who Dr. Zipfel treated for a ruptured brain AVM
June 6, 2018
St. Louis NBC affiliate, KSDK, highlights the care of a 25 year old woman who Dr. Zipfel treated for a ruptured brain AVM
May 11, 2018
Neurosurgeon dedicated to making surgeries smaller, less invasive
June 20, 2016
Barnes-Jewish Hospital blog highlighting Dr. Zipfel's use of minimally invasive surgical approaches
February 6, 2012
- SPECIAL THANKS
We are indebted to our patients, benefactors, and funding sources that make our work possible.
Harrington / Zhou Research Fund
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