Research Activities

Inhibiting Oxidative Phosphorylation In Vivo Restrains Th17 Effector Responses and Ameliorates Murine Colitis
Franchi L, Monteleone I, Hao LY, Spahr MA, Zhao W, Liu X, Demock K, Kulkarni A, Lesch CA, Sanchez B, Carter L, Marafini I, Hu X, Mashadova O, Yuan M, Asara JM, Singh H, Lyssiotis CA, Monteleone G, Opipari AW, Glick GD. Journal of Immunology (2017)
Abstract | PDF

Glioblastoma therapy can be augmented by targeting IDH1-mediated NADPH biosynthesis
Wahl DR, Dresser J, Wilder-Romans K, Parsels JD, Zhao SG, Davis M, Zhao L, Kachman M, Wernisch S, Burant CF, Morgan MA, Feng FY, Speers C, Lyssiotis CA, Lawrence TS. Cancer Research (2016) [Epub ahead of print]
Abstract | PDF

Pancreatic Stellate Cells Support Tumour Metabolism Through Autophagic Alanine Secretion
Sousa CM, Biancur DE, Wang X, Halbrook CJ, Sherman MH, Zhang L, Kremer D, Hwang RF, Witkiewicz AK, Ying H, Asara JM, Evans RM, Cantley LC, *Lyssiotis CA [*co-senior authors], *Kimmelman AC. Nature (2016) 25, 479483.

Highlighted in Nature (2016). Cancer metabolism: Friendly neighbours feed tumour cells | PDF
Highlighted in Science Signaling (2016). PDAC puts its neighbors to work | Article
Highlighted in Nature Reviews Cancer (2016). Feeding your friends | PDF
Highlighted in Nature Reviews Gastroenterology & Hepatology (2016)Pancreatic cancer: Stromal ... | PDF
Highlighted in Cancer Discovery (2016). Autophagic Pancreatic Stellate Cells Promote Pancreatic... | Article

Adipocytes Promote Pancreatic Cancer Cell Proliferation via Glutamine Transfer
Meyer KA, Neeley CK, Baker NA, Washabaugh AR, Flesher CG, Nelson BS, Frankel TL, Lumeng CN, Lyssiotis CA, Wynn ML, Rhim AD, O’Rourke RW. Biochemistry and Biophysics Reports (2016) 7, 144149.

Glutathione Biosynthesis is a Metabolic Vulnerability in PI(3)K/Akt-driven Breast Cancer
Lien EC, Lyssiotis CA, Juvekar A, Hu H, Asara JM, Cantley LC, Toker A. Nat Cell Biol. (2016) 18, 572578.

Phosphoinositide 3-kinase inhibitors induce DNA damage through nucleoside depletion
Juvekar A, Hu H, Yadegarynia S, Lyssiotis CA, Ullas S, Lien EC, Bellinger G, Son J, Hok RC, Seth P, Daly MB, Kim B, Scully R, Asara JM, Cantley LC, Wulf GM. PNAS (2016) 113, E4338E4347.

Identification of a Small Molecule Inhibitor of 3-Phosphoglycerate Dehydrogenase to Target Serine Biosynthesis in Cancers
Mullarky E, Luckio NC, Zavareh RB, Anglin J, Gomes AP, Nicolay BN, Wong JCY, Christen S, Takahashi H, Singh PK, Blenis J, Warren JD, Fendt SM, Asara JM, DeNicola GM, *Lyssiotis CA [co-senior authors], *Lairson LL, *Cantley LC. PNAS (2016) 113, 1778–1783.

            Highlighted by Science DailyTeam Finds New Approach to Curbing Cancer Growth | Article
Phosphoinositide 3-Kinase Regulates Glycolysis Through an AKT-independent Mechanism that Mobilizes Aldolase A Release from the Actin Cytoskeleton
Hu H, Juvekar A, Lyssiotis CA, Lien EC, Albeck JG, Varma G, Hung YP, Wang X, Ullas S, Tolan DR, Grant AK, Asara JM, Cantley LC, Wulf GM. Cell (2016) 164, 433–446.

            Highlighted in Cancer Discovery. PI3K Promotes Glycolysis through Release of Cytoskeletal Aldolase | Article

Targeting Glutamine Metabolism Sensitizes Pancreatic Cancer to PARP1-driven Metabolic Catastrophe Induced by ß-lapachone
Chakrabarti G, Moore Z, Luo X, Ilcheva M, Ali A, Anderson GG, Padanad M, Scaglioni PP, Cantley LC, Kimmelman AC, DeBerardinis RJ, *Lyssiotis CA [co-senior authors], *Boothman DA. Cancer & Metabolism (2015) 3, 12.

            Most read paper in Cancer & Metabolism, 2015.

A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Metastatic, Developmental, and Metabolic Characteristics
Sadanandam A, Wullschleger S, Lyssiotis CA, Grötzinger C, Barbi S, Bersani S, Körner J, Wafy I, Mafficini A, Lawlor RT, Asara JM, Blaker H, Cantley LC, Wiedenmann B, Scarpa A, Hanahan D. Cancer Discovery (2015) 5, 1296–1313.

Triomics Analysis of Imatinib-Treated Myeloma Cells Connects Kinase Inhibition to RNA Processing and Decreased Lipid Biosynthesis
Breitkopf SB, Yuan M, Helenius K, Lyssiotis CA, Asara JM. Analytical Chemistry (2015) 87, 10995–11006.

Methods for Diagnosing and Treating Oncogenic Kras-Associated Cancer. 
DePinho R, Cantley LC, Kimmelman A, Ying H, Lyssiotis CA. U.S. Patent Number 2015/0126580, filed December 20, 2011 and issued May 7, 2015. International Patent Number 14/367,341, filed June 20, 2014.

Targeting the Glutamine to Pyruvate Pathway for Treatment of Oncogenic Kras-Associated Cancer
Kimmelman AC, Son J, Cantley LC, Lyssiotis CA. U.S. Patent Number 2015/0110773, filed May 23, 2013 and issued April 23, 2015.

Targeting Increased Anaplerotic Metabolism of Pathogenic T Cells to Treat Immune Disease
Glick GD, Rossignol R, Lyssiotis CA, Wahl D, Lesch C, Sanchez B, Liu X, Hao LY, Taylor C, Hurd A, Ferrara JL, Tkachev V, Byersdorfer C, Boros L, Opipari AW. J. Pharmacol. Exp. Ther. (2014) 351, 298–307.

Oncogene Ablation-Resistant Pancreatic Cancer Cells Depend on Mitochondrial Function
Viale A, Pettazzoni P, Lyssiotis CA, Ying H, Sanchez N, Marchesini M, Carugo A, Green T, Seth S, Giuliani V, Kost-Alimova M, Muller F, Colla S, Nezi L, Genovese G, Deem AK, Kapoor A, Carugo A, Yao W, Brunetto E, Kang Y, Yuan M, Asara JM, Wang YA, Heffernan TP, Kimmelman AC, Wang H, Fleming J, Cantley LC, DePinho R, Draetta G. Nature (2014) 30, 628–632.
Abstract | PDF | Extended Figures | Times cited: 164

Highlighted in Nature Reviews Clinical Oncology (2014). Targeting Mitochondria in Pancreatic Cancer | PDF
Highlighted in Cancer Discovery (2014). Resistant PDAC Cells Require Mitochondrial Activity | Abstract
Highlighted by MDACC. Researchers Discover a Metabolic Mechanism for Resistant Pancreatic Cancer | Article

Colorectal Cancer Classification with Differential Prognosis and Personalized Therapeutic Responses
Hanahan D, Gray J, Sadanandam A, Lyssiotis CA. International Patent Number WO2014080381 A1, filed November 26, 2013 and issued May 30, 2014.

A Regenerative Approach to the Treatment of Multiple Sclerosis
Deshmukh VA, Tardif V, Lyssiotis CA, Green CC, Kerman B, Kim HJ, Padmanabhan K, Swoboda JG, Ahmad I, Kondo T, Gage FH, Theofilopoulos AN, Lawson BR, Schultz PG, Lairson LL. Nature (2013) 502, 327–32. 

Selected as the best science paper in MS in 2013. Multiple Sclerosis (2014) | PDF
Highlighted by The Gaurdian. Parkinson's Drug Could Prove to be New Treatment for Multiple Sclerosis | Article
Highlighted by U~T San Diego. Parkinson's Drug Holds Promise for MS | Article
Highlighted by TSRI. New Strategy to Treat Multiple Sclerosis Shows Promise in Mice | Article
Highlighted in Nature Reviews Drug Discovery (2013). Parkinson's Drug Promotes Myelin Repair | PDF
Highlighted in Nature Reviews Neurology (2013). Drug-enhanced Remyelination in a Multiple Sclerosis Model | Abstract
Highlighted in Nature Chemical Biology (2013). Reversing MS | PDF
Highlighted in Nature (2013). An Old Drug Plays a New Trick | PDF

Directed Differentiation of Oligodendrocytes Precursor Cells into a Myelinating Cell Fate
Deshmukh V, Lyssiotis CA, Lairson LL, Schultz PG. International Patent Number WO/2012/112933, filed February 17, 2012 and issued February 6, 2014.

FoxO3 Coordinates Metabolic Pathways to Maintain Redox Balance in Neural Stem Cells
Yeo H, Lyssiotis CA, Zhang Y, Ying H, Asara JM, Cantley LC, Paik JH. The EMBO Journal (2013) 32, 2589–602. 

Protein-Tyrosine Phosphatase 1B Regulates Pyruvate Kinase M2 Tyrosine Phosphorylation
Bettaieb A, Bakke J, Nagata N, Matsuo K, Xi Y, Liu S, AbouBechara D, Melhem R, Stanhope K, Cummings B, Graham J, Bremer A, Zhang S, Lyssiotis CA, Zhang Z-Y, Cantley LC, Havel PJ, Haj FG. Journal of Biological Chemistry (2013) 288, 17360–17371. 

A Colorectal Cancer Classification System that Associates Cellular Phenotype and Responses to Therapy
Sadanandam A, Lyssiotis CA, Homicsko K, Collisson EA, Gibb WJ, Wullschleger S, Ostos LC, Lannon WA, Grotzinger C, Del Rio M, Lhermitte B, Olshen AB, Wiedenmann B, Cantley LC, Gray JW, Hanahan D. Nature Medicine (2013) 19, 619–625. 

Highlighted in Nature Reviews Cancer (2013). Colorectal Cancer Classifications | PDF
Highlighted in Nature Reviews Clinical Oncology (2013). Turning Up Trumps for New CRC Subtypes | PDF

Glutamine Supports Pancreatic Cancer Growth Through a KRAS-Regulated Metabolic Pathway
*Son J, *Lyssiotis CA [*co-lead authors], Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, Kang Y, Fleming JB, Bardeesy N, Asara JM, Haigis MC, DePinho RA, Cantley LC, Kimmelman AC. Nature (2013) 496, 101–105.

Highlighted in Nautre Biotechnology (2013). Cancer Metabolism in Breadth and Depth | PDF 
Highlighted in Nature Reviews Cancer (2013). Glutamine Connections to Oncogene Alterations | PDF 
Highlighted in Cancer Discovery (2013). KRAS Reprograms Glutamine Metabolism in Pancreatic Cancer | PDF
Highlighted in Nature Reviews Gastroenterology and Hepatology (2013). Novel Pathway Identified... | PDF
Highlighted by Dana Farber. Scientists Find Potential Loophole in Pancreatic Cancer Defenses | Article

ERK1/2-Dependent Phosphorylation and Nuclear Translocation of PKM2 Promotes the Warburg Effect
Yang W, Zheng Y, Xia Y, Ji H, Chen X , Guo F, Lyssiotis CA, Aldape K, Cantley LC, Lu Z. Nature Cell Biology (2012) 14, 1295–1304. 

Highlighted in Nature Reviews Cancer (2012). Metabolism: Nuclear Functions | PDF 
Highlighted by Science Daily. Metabolic Protein Launches Sugar Feast That Nurtures Brain Tumors | Article

Influence of Threonine Metabolism on S-Adenosyl-Methionine and Histone Methylation
Shyh-Chang N, Locasale J, Lyssiotis CA, Zhang Y, Teo RY, Onder T, Unternaehrer J, Ratanasirintrawoot S, Zhu H, Asara JM, Daley GQ, Cantley LC. Science (2012) 339, 222–226.

Highlighted in Science (2012). When Metabolism and Epigenetics Converge | PDF

Combining a PI3K Inhibitor with a PARP Inhibitor Provides an Effective Therapy for BRCA1–Related Breast Cancer
Juvekar A, Burga L, Hu H, Lunsford E, Ibrahim YH, Balmana J, Rajendran A, Papa A, Spencer K, Lyssiotis CA, Nardella C, Pandolfi PP, Baselga J, Scully R, Asara JM, Cantley LC, Wulf GM. Cancer Discovery (2012) 2, 1049–1063. 

Highlighted in Nature Reviews Cancer (2012). Therapeutics: PI3K–PARP Combination | PDF
Highlighted in Cancer Discovery (2012). Combining Inhibition of PI3K and PARP as Cancer Therapy | PDF

Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose Metabolism
*Ying H, *Kimmelman AC, *Lyssiotis CA [*co-lead authors], Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, Yan H, Wang W, Chen S, Viale A, Zheng H, Paik J, Lim C, Guimaraes AR, Martin ES, Chang J, Hezel AF, Perry SR, Hu J, Gan B, Xiao Y, Asara JM, Weissleder R, Wang YA, Chin L, Cantley LC, DePinho RA. Cell (2012) 149, 656–670. 

Cell 20-most read articles, May 2012 Exceptional article [12], as evaluated by Faculty of 1000 | Link
Highlighted in Nature Reviews Clinical Oncology (2012). Mouse Models Link Metabolism... | PDF
Highlighted in Cancer Research (2012). Metabolic Pathways Controlling KRAS-driven Pancreatic Cancer | PDF
Highlighted in Science Business eXchange (2012). Kras in Cancer Metabolism | PDF
Highlighted by MD Anderson. Mutant Kras Drives Pancreatic Cancer Maintenance via Metabolic Pathways | Article
Highlighted by Dana Farber. Advanced Pancreatic Tumors Depend on Continued Oncogene Activity | Article

mTOR Drives its Own Activation via SCFβ-TRCP-dependent Degradation of the mTOR Inhibitor DEPTOR
Gao D, Inuzuka H, Tan MM, Fukushima H, Locasale JW, Liu P, Wan L, Zhai B, Chin YR, Shaik S, Lyssiotis CA, Gygi SP, Toker A, Cantley LC, Asara JM, Harper JW, Wei W. Molecular Cell (2011) 44, 290–303. 

Highlighted in Nature Reviews Molecular Cell Biology (2011). mTOR Targets its Own Inhibitor | PDF
Highlighted by Science News Line (2012). Unraveling the Complex Signaling... | Article

Phosphoglycerate Dehydrogenase Diverts Glycolytic Flux and Contributes to Oncogenesis
Locasale JW, Grassian AR, Melman T, Lyssiotis CA, Mattaini KR, Bass AJ, Heffron G, Metallo CM, Muranen T, Sharfi H, Sasaki AT, Anastasiou D, Mullarky E, Vokes NI, Sasaki M, Beroukhim R, Stephanopoulos G, Ligon AH, Meyerson M, Richardson AL, Chin L, Wagner G, Asara JM, Brugge JS, Cantley LC, Vander Heiden MG. Nature Genetics (2011) 43, 869–874.

Highlighted in Nature Reviews Cancer (2011). Flexible Flux | PDF
Highlighted in Science Business eXchange (2011). PHGDH | Article
Highlighted in Nature Biotechnology (2011). Spotlight on Serine Metabolism in Cancer | Article
Highlighted in Cell Metabolism (2011). Serine Metabolism: Some Tumors Take the Road Less Traveled | PDF
Highlighted in Pigment Cell Melanoma Research (2011). Serine biosynthesis | PDF

A Cross-Species Analysis of a Mouse Model of Breast Cancer-Specific Osteolysis and Human Bone Metastases Using Gene Expression Profiling
Sadanandam A, Futakuchi M, Lyssiotis CA, Gibb WJ, Singh RK. BMC Cancer (2011) 11, 304-317. 

Pan-Src Family Kinase Inhibitors Replace Sox2 During the Direct Reprogramming of Somatic Cells
*Staerk J, *Lyssiotis CA [*co-lead authors], Medeiro LA, Bollong M, Foreman RK, Zhu S, Garcia M, Gao Q, Bouchez LC, Lairson LL, Charette BD, Supekova L, Janes J, Brinker A, Cho CY, Jaenisch R, Schultz PG. Angew. Chem. Int. Ed. (2011) 50, 5734–5736. 

A Genomic Screen Identifies TYRO3 as a MITF Regulator and Melanoma Oncogene
Zhu S, Wurdak H, Wang Y, Galkin A, Tao H, Li J, Lyssiotis CA, Yan F, Tuu B, Miraglia L, Walker J, Sun F, Orth A, Harris J, Schultz PG, Wu X. PNAS (2009) 106, 17025–17030. 

Bz-423 Superoxide Signals B Cell Apoptosis via Mcl-1, Bak, and Bax
Blatt NB, Boitano AE, Lyssiotis CA, Opipari AW, Glick GD. Biochem. Pharmacology (2009) 78, 966–973. 

Reprogramming of Murine Fibroblasts to iPS Cells With Chemical Complementation of Klf4
*Lyssiotis CA, *Foreman RK, *Staerk J [*co-lead authors], Garcia M, Mathur D, Markoulaki S, Hanna J, Lairson LL, Charette BD, Bouchez L, Bollong M, Kunick C, Brinker A, Cho CY, Schultz PG, Jaenisch R. PNAS (2009) 106, 8912–8917. 

PNAS 50-most read articles, June 2009 Highlighted in Regenerative Medicine (2009) | PDF
Highlighted in Nature Cell Biology (2009). Chemical iPS Cocktails | PDF
Highlighted in Assay and Drug Development Technologies (2009). Discovering Pluripotent Compounds | PDF
Highlighted in Nature Reports (2009). New Types of ES Cells Generated by Stabilizing Pluripotency | Article

A Small Molecule Primes Embryonic Stem Cells for Differentiation
Zhu S, Wurdak H, Wang J, Lyssiotis CA, Peters EC, Cho CY, Wu X, Schultz PG. Cell Stem Cell (2009) 4, 416–426. 

Highlighted in Nature Chemical Biology (2009). Endowing Endoderm | PDF
Highlighted in Cell Stem Cell (2009). Using Small Molecules to Great Effect in Stem Cell Differentiation | PDF
Highlighted in Molecular Interventions (2009). Stauprimide: A Small Molecule Directs Stem Cells to Differentiate | PDF

Bz-423 Superoxide Signals Apoptosis via Selective Activation of JNK, Bak, and Bax

Blatt NB, Boitano AE, Lyssiotis CA, Opipari AW, Glick GD. Free Radical Biology Med. (2008) 45, 1232–1242. 

Inhibition of Histone Deacetylase Activity Induces Developmental Plasticity in Oligodendrocyte Precursor Cells
Lyssiotis CA, Walker J, Wu C, Kondo T, Schultz PG, Wu X. PNAS (2007) 104, 14982–14987. 

Highlighted in Cell (2007). Leading Edge: Glial Precursors Break Their Commitment | PDF

A Novel Benzodiazepine Increases the Sensitivity of B Cells to Receptor Stimulation with Synergistic Effects on Calcium Signaling and Apoptosis
Bednarski JJ, Lyssiotis CA, Roush RR, Boitano AE, Glick GD, Opipari AW. J. Biol. Chem. (2004) 279, 29615–29621.