Taub Institute: Genomics Core
AN NIA-FUNDED ALZHEIMER'S DISEASE RESEARCH CENTER

 

Columbia University
Medical Center
Neurological Institute

710 West 168th Street, 3rd floor
(212) 305-1818


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About Us

Taub Faculty

Laura Beth J. McIntire, PhD

Laura Beth J. McIntire, PhD

Assistant Professor of Pathology & Cell Biology at CUMC

Email: lbm2110@cumc.columbia.edu

I have been studying the molecular basis of Alzheimer’s disease (AD) as well as potential therapeutic targets with a focus on lipid biology. My research focus in lipid biology was strongly influenced through my work dissecting the role of phosphatidic acid-preferring phospholipase A1 in brain as a research assistant, in the lab of John Glomset, a Howard Hughes Medical Institute Investigator (1999-2001). Building on my interest of lipid modifying enzymes for my doctoral thesis (2001 – 2006), I was the first to discover and characterize a novel lipid kinase, Multi-substrate Lipid Kinase later renamed Acylglycerol Kinase (MuLK/AGK). For my postdoctoral training (2006 – 2009), I chose to apply my expertise in lipid biology to a clinical application with severe unmet need, determining the role of lipids and lipid modifying enzymes in Alzheimer’s disease (AD). During the past 11 years at Columbia University Medical Center (CUMC), which included my postdoctoral training, promotion to Associate Research Scientist (2009) and appointment to Assistant Professor (2014), I have been investigating mechanisms underlying the pathogenesis of AD including identifying novel molecules and harnessing their potential as therapeutic targets in AD.

Specifically, I’ve focused on the role of phosphoinositides in AD studying both the major phosphatidylinositide 4,5-bisphosphate [PI(4,5)P2] phosphatase in the brain, Synaptojanin1 (Synj1), as well as the family of phosphoinositide 3-kinases. I’ve found that maintenance of PI(4,5)P2 is critical for synapse maintenance and abrogation of behavioral impairments in a mouse model of the disease (McIntire et al., 2012). I’ve also developed an assay amenable to High Throughput Screening (HTS) for identification of Synj1 inhibitors (McIntire et al., 2014). In order to identify new tractable targets in AD, I’ve characterized mouse embryonic stem cell derived pyramidal neurons (mESN) as a screening platform for AD phenotypes including Aβ biogenesis and synapse loss (McIntire et al., 2013). With this neuornal model I used RNAi to target phosphoinositide metabolism to identify new lipid modifying enzymes capable of preventing Aβ-triggered synapse loss in addition to Synj1. I am currently engaging in lipidomic studies which may validate specific lipid species as emerging and highly promising targets in AD.

I've also been pursuing the validation of putative drug targets by investigating mechanism of action and in vivo studies of a novel compound class identified in a small molecule screen using an in vitro, cell based assay for β-site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) regulators. I continue to validate hits including a novel monoamine transporter which is the subject of a Mentored Research Scientist Development Award (K01, 2014-2019). I have expertise in identifying and validating novel cellular pathways as potential future therapeutic targets in AD with a focus in lipid biology and stem cell modeling. I am dedicated to discovering the role of novel cellular targets in AD pathogenesis and progression with the intent to pharmacologically harness them for amelioration of this devastating disease.

Awards and Honors:

Mentored Research Scientist Development Award (K01), NIH/NIA, 07/01/2014 – 06/30/2019 K01, The role of a novel atypical monoamine transporter in Alzheimer's disease

Alzheimer's Association New Investigator Research Grant (NIRG) 07/01/2016 – 06/30/2018 Functional genetic screen for lipid modifying enzymes in AD synapse loss

Exploratory/Developmental Research Grant (R21), NIH/NINDS, 07/01/2014 – 06/30/2017 Screening lipid modifying enzymes to ameliorate A-beta triggered synaptic loss

2017 Columbia Lipid Symposium Selected Abstract Oral Presentation 03/24/2017 Role for lipid modifying enzymes in Alzheimer/s disease-associated synaptic loss CUMC, NY, NY

Alzheimer/s Association International Conference Invited Oral Presentation Developing Topics 07/27/2016 Plasma Membrane Monoamine Transporter Modulates BACE1 Activity, Toronto ON, CA

Platform Presentation and Best Abstract Award – Columbia University Pathology and Cell Biology 2015 Translational Research Retreat 09/10/2015 High Throughput Chemical Genetics Screen for Soluble Amyloid Precursor Protein-β Identifies Plasma Membrane Monoamine Transporter as a Regulator of BACE1, CUMC, NY, NY

Alzheimer's Association, New Investigator Research Grant (NIRG), 11/01/2010 – 10/31/2012 Dissecting the role of PI3K family members in Aβ biogenesis Irving Institute for Clinical and Translational Research Pilot Grant, 07/01/2010 – 06/30/2011 In vivo efficacy of a new class of CNS targeted amyloid lowering compounds

Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Alzheimer's Disease Research Center (ADRC), Pilot Grant, 06/01/2009 – 05/31/2010 A novel kinase target in Alzheimer's disease



*Previously Johnson LB

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