Overview

One of the main areas of research within my group involves identifying and characterizing specific transport proteins that are required by cells to fulfill their metabolic needs. Within this objective, we aim to understand what drives selective transporter expression in disease, how transporters function in specific physiological contexts, and how we can target the unique metabolic demands of cancer. We utilize biochemical and molecular biology techniques and develop quantitative mass spectrometry-based methods that include targeted and discovery metabolomics, stable-isotope tracing, and metabolic flux analysis to characterize the fate of key nutrients in diseased cells.

Publications

Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I.
Nature
DOI: 10.1038/s41586-020-2229-5
PubMed: 32376951
04/2020

Selective Alanine Transporter Utilization Creates a Targetable Metabolic Niche in Pancreatic Cancer.
Cancer discovery
DOI: 10.1158/2159-8290.cd-19-0959
PubMed: 32341021
04/2020

Deuterium Tracing to Interrogate Compartment-Specific NAD(P)H Metabolism in Cultured Mammalian Cells.
Methods in molecular biology (Clifton, N.J.)
DOI: 10.1007/978-1-0716-0159-4_4
PubMed: 31893370
01/2020

KRAS4A directly regulates hexokinase 1.
Nature
DOI: 10.1038/s41586-019-1832-9
PubMed: 31827279
12/2019

Glutamine metabolism via glutaminase 1 in autosomal-dominant polycystic kidney disease.
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
DOI: 10.1093/ndt/gfx349
PubMed: 29420817
08/2018

Posttranscriptional Upregulation of IDH1 by HuR Establishes a Powerful Survival Phenotype in Pancreatic Cancer Cells.
Cancer research
DOI: 10.1158/0008-5472.can-17-0015
PubMed: 28652247
06/2017

LKB1 promotes metabolic flexibility in response to energy stress.
Metabolic engineering
DOI: 10.1016/j.ymben.2016.12.010
PubMed: 28034771
12/2016

Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models.
Nature medicine
DOI: 10.1038/nm.4181
PubMed: 27643638
09/2016

Distinct Metabolic States Can Support Self-Renewal and Lipogenesis in Human Pluripotent Stem Cells under Different Culture Conditions.
Cell reports
DOI: 10.1016/j.celrep.2016.06.102
PubMed: 27477285
07/2016

Reductive carboxylation supports redox homeostasis during anchorage-independent growth.
Nature
DOI: 10.1038/nature17393
PubMed: 27049945
04/2016

Chasing One-Carbon Units to Understand the Role of Serine in Epigenetics.
Molecular cell
DOI: 10.1016/j.molcel.2016.01.006
PubMed: 26799763
01/2016

Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism.
Nature communications
DOI: 10.1038/ncomms9784
PubMed: 26522426
11/2015

Metabolic consequences of oncogenic IDH mutations.
Pharmacology & therapeutics
DOI: 10.1016/j.pharmthera.2015.05.003
PubMed: 25956465
05/2015

Regulation of substrate utilization by the mitochondrial pyruvate carrier.
Molecular cell
DOI: 10.1016/j.molcel.2014.09.024
PubMed: 25458843
10/2014

Tracing compartmentalized NADPH metabolism in the cytosol and mitochondria of mammalian cells.
Molecular cell
DOI: 10.1016/j.molcel.2014.05.008
PubMed: 24882210
05/2014

IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism.
Cancer research
DOI: 10.1158/0008-5472.can-14-0772-t
PubMed: 24755473
04/2014

Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells.
Nature
DOI: 10.1038/nature12138
PubMed: 23665962
05/2013

Identification and mechanistic studies of a novel ubiquitin E1 inhibitor.
Journal of biomolecular screening
DOI: 10.1177/1087057111433843
PubMed: 22274912
01/2012

Largazole and its derivatives selectively inhibit ubiquitin activating enzyme (e1).
PloS one
DOI: 10.1371/journal.pone.0029208
PubMed: 22279528
01/2012

Research

Better tools to study amino acid metabolism and transport in intact cells
There are ~450 solute carrier (SLC) transporters that participate in the import and efflux of ions, amino acids, sugars, and cofactors required for metabolism. However, over 30% of
these SLCs are uncharacterized or poorly understood. Our research group is currently developing better molecular biology, imaging, and metabolomics tools that aim to advance our understanding of the function, localization, and cooperativity of amino acid transporters through uncoupling of transport from intracellular metabolism.

Understand the metabolic advantage of selective, compartment-specific enzyme expression
The metabolic pathways that comprise eukaryotic metabolism are compartmentalized into distinct and specialized organelles (e.g. mitochondria, lysosomes, peroxisomes). Current metabolomics methods that extract bulk cellular metabolites fail to capture the compartmentalization of
intracellular metabolism. Our group aims to develop better methods to interrogate compartmentalized metabolic pathways. In this vein, we hope to understand how expression of specific enzyme isoforms may offer a selective advantage for cancer cells.

Metabolic and transporter dependencies in childhood leukemia
Therapies that target the unique metabolism of leukemic blasts have demonstrated remarkable clinical success. However, toxicities can often limit the efficacy of anti-metabolic therapies
and relapse of therapeutic-resistant cancer can occur. My group aims to identify metabolic dependencies in childhood leukemia with a specific focus on relapsed cases. Furthermore, we are interested in targeting metabolite transport as a more direct approach over systemic metabolite depletion therapies that are currently employed.

Honours & Awards

American Cancer Society Postdoctoral Fellowship (2019-2020)

Siebel Scholar (2016)

Achievement Reward for College Scientists (2016)