Justin Lathia, PhD
Staff
Director of Faculty Development
Vice Chair, Department of Cardiovascular & Metabolic Sciences
Email: [email protected]
Location: Cleveland Clinic Main Campus
Research
We are interested in the biology of maligant brain tumors, namely glioblastoma. We have active projects in cell adhesion mechanisms, cell-cell communication, and the interaction between tumor cells and the immune system. We also investigate sex differences in glioblastoma.
Biography
Dr. Justin Lathia leads a translational cancer stem cell research laboratory and is Vice Chair and Professor in the Department of Cardiovascular & Metabolic Sciences at the Lerner Research Institute (LRI), part of the Cleveland Clinic and also serves as the Director of Faculty Development for the LRI. Dr. Lathia is also the Scientific Director of the Rose Ella Burkhardt Brain Tumor & Neuro-Oncology Center at the Cleveland Clinic and the Melvin Burkhardt Endowed Chair in Neuro-Oncology Research. He is also the Reza Khatib MD Professor, and Co-Leader of the Molecular Oncology Program at the Case Comprehensive Cancer Center.
Dr. Lathia is a native of central Pennsylvania and received a B.S. and M.S. from Drexel University in Philadelphia, PA in 2003. While at Drexel, he developed targeted ultrasound contrast agents which preferentially bound to newly formed vessel in breast cancer models. After graduation from Drexel, Dr. Lathia completed his Ph.D. as part of the NIH-Cambridge Graduate Partnership Program. His work focused on the role of cell adhesion molecules during the development of the nervous system. After completing his Ph.D. in 2008 he completed post-doctoral fellowships at Duke and the Cleveland Clinic where he focused on the role of cell adhesion in regulating cancer stem cells in brain tumors. In 2012, Dr. Lathia moved to the Department of Cardiovascular and Metabolic Sciences as an independent investigator and the work in his lab focuses on how the stem cell state is regulated in advanced cancers. Projects in the Lathia laboratory involve understanding how cancer stem cells interact with their surrounding microenvironment as well as one another with the goal of identifying unique pathways for therapeutic development. Work in the Lathia laboratory has resulted in a Phase 1 clinical trial aimed at targeting myeloid-derived suppressor cells that interact with cancer stem cells to suppress the immune system in glioblastoma.
Dr. Lathia has co-authored over 250 publications and work in his lab is currently supported by multiple National Institutes of Health grants and foundation grants. Dr. Lathia also contributes as a peer reviewer to over 155 journals, serves on the editorial board for Cell Reports, Cancer Research, and Neuro-Oncology, has served on multiple grant review panels for the National Institutes of Health and private foundations. He recently served as a co-editor for a cancer stem cell textbook. Dr. Lathia also serves as a co-organizer for the cancer stem cell meeting held in Cleveland in 2014, 2016, 2018, and 2022. At each meeting, the three-day event drew over 300 attendees from over 25 states and 15 countries.
Education & Professional Highlights
Appointed
2010
Education & Fellowships
Fellowship - Cleveland Clinic
Neuro-Oncology
Cleveland, OH USA
2009
Fellowship - Duke University
Neuro-Oncology
Durham, NC USA
2008
Graduate Education - University of Cambridge (via NIH-Cambridge Graduate Partnership Program)
Ph.D., Stem Cell Biology, Neurology
Cambridge, UK
2008
Graduate School - Drexel University
M.S., Biomedical Engineering
Philadelphia, PA USA
2003
Undergraduate - Drexel University
B.S., Biomedical Engineering
Philadelphia, PA USA
2003
Research
Our main area of interest is understanding interactions within the glioblastoma tumor microenvironment that drive tumor progression. Currently, we focus on adhesion and cell-cell communication mechanisms utilized by cancer stem cells to promote their maintenance, tumor cell-immune cell interactions that drive tumorigenesis, and the contribution of metabolites, including those derived from the gut microbiome, to GBM progression. Our laboratory studies range from basic, mechanistic studies on cancer stem cell pathways and tumor microenvironment interactions to translational studies that interrogate patient samples
Adhesion and cell-cell communication
Cells are driven by two main cues, an intrinsic and extrinsic program. Within the extrinsic programs, we are interested in how tumor cells interact with one another and the specialized extracellular matrix present in the tumor microenvironment. Specifically, we have projects focused on the adhesion protein junctional adhesion molecule A and the connexin proteins that mediate cell-cell communication through gap junctions. These interactions drive stem cell maintenance and may represent a new therapeutic angle for tumors.
Tumor-immune cell interactions
Attempts to alter immune activation have been successful in other advanced cancers, but a series of diverse strategies has yet to markedly increase glioblastoma patient survival. We have shown that immunosuppressive myeloid-derived suppressor cells (MDSCs) correlate with poor GBM prognosis, drive cancer stem cell function, and interact with the tumor through multiple signaling networks that can be neutralized to increase immune activation.
Sex differences in glioblastoma
Within our study of MDSCs, we also interrogated MDSC subsets to reveal differences in localization and function in a sex-specific manner and identified sex-specific MDSC subset signaling programs that can be altered to increase immune activation and decrease GBM growth. We are currently investigating sex differences in other immune cell compartments.
Our Team
Selected Publications
View publications for Justin Lathia, PhD
(Disclaimer: This search is powered by PubMed, a service of the U.S. National Library of Medicine. PubMed is a third-party website with no affiliation with Cleveland Clinic.)
Mitchell Kelly, Sprowls Samuel A, Shakya Sajina, Silver Daniel J, Goins Christopher M, Wallace Lisa, Roversi Gustavo, Schafer Rachel, Kay Kristen, Lauko Adam, Kashyap Anjali, D'Amato Kass Jonathan, Mulkearns-Hubert Erin E, Johnson Sadie, Alvarado Joseph, Stauffer Shaun R, Hubert Christopher G, Lathia Justin D. WDR5 represents a therapeutically exploitable target for cancer stem cells in glioblastoma. Genes Dev. 2023. 36732025.
Sprowls Samuel A, Lathia Justin D. Breaking down the barrier to medulloblastoma treatment: Piezo2 knockout disrupts the BTB and increases vascular permeability. Neuron. 2023. 36603549.
Lathia Justin. Plasma IL13Rα2 as a novel liquid biopsy biomarker for glioblastoma. J Neurooncol. 2022. 36436150.
Bharti Rashmi, Dey Goutam, Lin Feng, Lathia Justin, Reizes Ofer. CD55 in cancer: Complementing functions in a non-canonical manner. Cancer Lett. 2022. 36216147.
Chambers Laura M, Esakov Rhoades Emily L, Bharti Rashmi, Braley Chad, Tewari Surabhi, Trestan Lexie, Alali Zahraa, Bayik Defne, Lathia Justin D, Sangwan Naseer, Bazeley Peter, Joehlin-Price Amy S, Wang Zeneng, Dutta Sumita, Dwidar Mohammed, Hajjar Adeline, Ahern Philip P, Claesen Jan, Rose Peter, Vargas Roberto, Brown J Mark, Michener Chad M, Reizes Ofer. Disruption of the Gut Microbiota Confers Cisplatin Resistance in Epithelial Ovarian Cancer. Cancer Res. 2022. 36206317.
Bayik Defne, Bartels Cynthia F, Lovrenert Katreya, Watson Dionysios C, Kay Kristen, Lee Juyeun, Lauko Adam, Johnson Sadie, Lo Alice, Silver Daniel J, McGraw Mary, Grabowski Matthew, Mohammadi Alireza M, Scacheri Peter, Lathia Justin D. Distinct Cell Adhesion Signature Defines Glioblastoma Myeloid-Derived Suppressor Cell Subsets. Cancer Res. 2022. 36126163.
Lauko Adam, Volovetz Josephine, Turaga Soumya M, Bayik Defne, Silver Daniel J, Mitchell Kelly, Mulkearns-Hubert Erin E, Watson Dionysios C, Desai Kiran, Midha Manav, Hao Jing, Bao Shideng, Yu Jennifer S, Lathia Justin D. SerpinB3 drives cancer stem cell survival in glioblastoma. Cell Rep. 2022. 36103817.
Mulkearns-Hubert Erin E, Hajdari Nicole, Silver Daniel J, Hubert Christopher G, Mitchell Kelly, Shakya Sajina, Lathia Justin D. VRK1 Is a Synthetic-Lethal Target in VRK2-Deficient Glioblastoma. Cancer Res. 2022. 36069976.
Lee Juyeun, Bayik Defne, Lathia Justin D. Preinvasive to Invasive: PD-1-Expressing Macrophages Shift Lung Cancer into High Gear. Cancer Res. 2022. 35844171.
Bayik Defne, Lee Juyeun, Lathia Justin D. All Glioblastoma Are Not Equal: Distinct Spatial Immune Profiles Between De Novo and Recurrent Tumors. Cancer Immunol Res. 2022. 35670711.
Tewari Surabhi, Park Deborah Y J, Wei Wei, Chao Samuel T, Yu Jennifer S, Suh John H, Kilic Sarah, Peereboom David M, Stevens Glen H J, Lathia Justin D, Prayson Richard, Barnett Gene H, Angelov Lilyana, Mohammadi Alireza M, Murphy Erin S. Sex-Specific Differences in Low-Grade Glioma Presentation and Outcome. Int J Radiat Oncol Biol Phys. 2022. 35667529.
Tumor Treating Fields: killing two birds with one stone. J Clin Invest. 2022. 35426370.
Shin Junchul, Tkachenko Svyatoslav, Chaklader Malay, Pletz Connor, Singh Kanwardeep, Mitchell Kelly, Hu Bo, Lathia Justin D, Stenina-Adognravi Olga, Podrez Eugene, Byzova Tatiana V, Cherepanova Olga A. Endothelial OCT4 is atheroprotective by preventing metabolic and phenotypic dysfunction. Cardiovasc Res. 2022. 35325071.
Bayik Defne, Lee Juyeun, Lathia Justin D. The Role of Myeloid-Derived Suppressor Cells in Tumor Growth and Metastasis. Exp Suppl. 2022. 35165865.
Hubert Christopher G, Lathia Justin D. Seeing the GBM diversity spectrum. Nat Cancer. 2021. 35122081.
Mitchell Kelly, Lathia Justin D. Roadmap on plasticity and epigenetics in cancer. Phys Biol. 2022. 35078159.
Lee Juyeun, Troike Katie, Fodor R'ay, Lathia Justin D. Unexplored Functions of Sex Hormones in Glioblastoma Cancer Stem Cells. Endocrinology. 2022. 35023543.
Li Yaxin, Dano Raina, Li Cathy, Zhang Wenjing, Lathia Justin D, Wang Bingcheng, Su Bin. Pharmacokinetic and brain distribution study of an anti-glioblastoma agent in mice by HPLC-MS/MS. Biomed Chromatogr. 2022. 34981554.
Hubert Christopher, Lathia Justin Durla. Surgical resection of glioblastomas induces pleiotrophin-mediated self-renewal of glioblastoma stem cells in recurrent tumors. Neuro Oncol. 2022. 34964899.
Hine Christopher, Lathia Justin D. Early DNA damage detection and cellular autophagy as drivers of stress-adaptive HS production: A paradox resolved. Cell Chem Biol. 2021. 34919842.
Hubert Christopher G, Lathia Justin D. Identifying pediatric glioma's Achilles heel through rational combination therapies. Am J Cancer Res. 2021. 34873492.
Lathia Justin D. Cancer stem cells: advances in biology and clinical translation-a Keystone Symposia report. Ann N Y Acad Sci. 2021. 34850398.
Troike Katie M, Lathia Justin D. A Drosophila RNAi screen reveals conserved glioblastoma-related adhesion genes that regulate collective cell migration. G3 (Bethesda). 2022. 34849760.
Patil Nirav, Somasundaram Eashwar, Lathia Justin D, Buerki Robin A, Choi Serah, Sloan Andrew E, Barnholtz-Sloan Jill S. Independently validated sex-specific nomograms for predicting survival in patients with newly diagnosed glioblastoma: NRG Oncology RTOG 0525 and 0825. J Neurooncol. 2021. 34761331.
Watson Dionysios C, Johnson Sadie, Santos Akeem, Yin Mei, Bayik Defne, Lathia Justin D, Dwidar Mohammed. Scalable Isolation and Purification of Extracellular Vesicles from Escherichia coli and Other Bacteria. J Vis Exp. 2021. 34723953.
Lathia Justin D. All Damage Is Not Created Equal: Unraveling the Complexity of Sex Chromosomes and Hormones in the DNA Damage Response. Endocrinology. 2021. 34618897.
Silver Daniel J, Lathia Justin D, Hine Christopher. Hydrogen sulfide operates as a glioblastoma suppressor and is lost under high fat diet. Mol Cell Oncol. 2021. 34616877.
Troike Katie M, Alban Tyler J, Grabowski Matthew M, Otvos Balint, Lathia Justin D. The Translocator Protein () Genetic Polymorphism A147T Is Associated with Worse Survival in Male Glioblastoma Patients. Cancers (Basel). 2021. 34572751.
Wang Gi-Ming, Cioffi Gino, Waite Kristin A, Lanese Robert, Lathia Justin D, Barnholtz-Sloan Jill S. Importance of the intersection of age and sex to understand variation in incidence and survival for primary malignant gliomas. Neuro Oncol. 2022. 34387331.
Wightman Samantha M, Alban Tyler J, Chen Xing, Lathia Justin D, Wang Yuxin, Stark George R. Bazedoxifene inhibits sustained STAT3 activation and increases survival in GBM. Transl Oncol. 2021. 34365219.
Hou Yuan, Zhou Yadi, Gack Michaela U, Lathia Justin D, Kallianpur Asha, Mehra Reena, Chan Timothy A, Jung Jae U, Jehi Lara, Eng Charis, Cheng Feixiong. Multimodal single-cell omics analysis identifies epithelium-immune cell interactions and immune vulnerability associated with sex differences in COVID-19. Signal Transduct Target Ther. 2021. 34330889.
Lathia Justin D. Neutralizing shapeshifting pericytes enhances glioblastoma therapeutic efficacy. Cell Res. 2021. 34267351.
Silver Daniel J, Roversi Gustavo A, Bithi Nazmin, Wang Sabrina Z, Troike Katie M, Neumann Chase Ka, Ahuja Grace K, Reizes Ofer, Brown J Mark, Hine Christopher, Lathia Justin D. Severe consequences of a high-lipid diet include hydrogen sulfide dysfunction and enhanced aggression in glioblastoma. J Clin Invest. 2021. 34255747.
Lathia Justin, Liu Yehe. Development of an arteriolar niche and self-renewal of breast cancer stem cells by lysophosphatidic acid/protein kinase D signaling. Commun Biol. 2021. 34168243.
Bayik Defne, Lathia Justin D. Cancer stem cell-immune cell crosstalk in tumour progression. Nat Rev Cancer. 2021. 34103704.
Shakya Sajina, Gromovsky Anthony D, Hale James S, Prager Briana, Wallace Lisa C, Lathia Justin D, Brown J Mark, Hubert Christopher G. Altered lipid metabolism marks glioblastoma stem and non-stem cells in separate tumor niches. Acta Neuropathol Commun. 2021. 34059134.
Crean-Tate Katie K, Braley Chad, Dey Goutam, Esakov Emily, Trestan Alexandria, Silver Daniel J, Turaga Soumya M, DeBernardo Robert, Michener Chad M, Rose Peter G, Lathia Justin, Reizes Ofer. Pretreatment with LCK inhibitors chemosensitizes cisplatin-resistant endometrioid ovarian tumors. J Ovarian Res. 2021. 33888137.
Lee Juyeun, Kay Kristen, Troike Katie, Ahluwalia Manmeet S, Lathia Justin D. Sex Differences in Glioblastoma Immunotherapy Response. Neuromolecular Med. 2022. 33864598.
Lathia Justin D. Fountain of chaos: cerebrospinal fluid enhancement of cancer stem cells in glioblastoma. Neuro Oncol. 2021. 33749775.
Silver Daniel J, Lathia Justin D. Go, cancer stem cell, go! CSCs overcome myelin inhibition to move within white matter pathways. Brain. 2021. 33693693.
Mitchell Kelly, Lathia Justin D. A circuitous route to GBM stem cell signalling. Nat Cell Biol. 2021. 33664497.
Lauko Adam, Lo Alice, Ahluwalia Manmeet S, Lathia Justin D. Cancer cell heterogeneity & plasticity in glioblastoma and brain tumors. Semin Cancer Biol. 2022. 33640445.
Xu Jielin, Huang Yin, Zhou Yadi, Hou Yuan, Bekris Lynn M, Lathia Justin, Pieper Andrew A, Leverenz James B, Cheng Feixiong. Multimodal single-cell/nucleus RNA sequencing data analysis uncovers molecular networks between disease-associated microglia and astrocytes with implications for drug repurposing in Alzheimer's disease. Genome Res. 2021. 33627474.
Cheng Feixiong, Zhou Yadi, Martin William R, Hou Yuan, Castrillon Jessica A, Fang Jiansong, Lathia Justin D, Keri Ruth A, Eng Charis. Comprehensive characterization of protein-protein interactions perturbed by disease mutations. Nat Genet. 2021. 33558758.
Otvos Balint, Alban Tyler J, Grabowski Matthew M, Bayik Defne, Mulkearns-Hubert Erin E, Radivoyevitch Tomas, Rabljenovic Anja, Johnson Sarah, Androjna Charlie, Mohammadi Alireza M, Barnett Gene H, Ahluwalia Manmeet S, Lathia Justin D. Preclinical Modeling of Surgery and Steroid Therapy for Glioblastoma Reveals Changes in Immunophenotype that are Associated with Tumor Growth and Outcome. Clin Cancer Res. 2021. 33542075.
Li Yaxin, Orahoske Cody M, Bhattarai Asmita, Sabbagh Abboud, Bobba Viharika, Salem Fatma M, Zhang Wenjing, Shukla Girish C, Lathia Justin D, Wang Bingcheng, Su Bin. Small-Molecule HSP27 Inhibitor Abolishes Androgen Receptors in Glioblastoma. J Med Chem. 2021. 33523674.
Hitomi Masahiro, Chumakova Anastasia P, Silver Daniel J, Pontius W Dean, Murphy Stephanie, Anand Neha, Lathia Justin D. Asymmetric cell division promotes therapeutic resistance in glioblastoma stem cells. JCI Insight. 2021. 33351787.
Mulkearns-Hubert Erin E, Reizes Ofer, Lathia Justin D. Connexins in Cancer: Jekyll or Hyde? Biomolecules. 2020. 33321749.
Alban Tyler J, Bayik Defne, Lathia Justin D. High-Dimensional Analysis of Circulating and Tissue-Derived Myeloid-Derived Suppressor Cells from Patients with Glioblastoma. Methods Mol Biol. 2021. 33237547.
Mitchell Kelly, Troike Katie, Silver Daniel J, Lathia Justin D. The evolution of the cancer stem cell state in glioblastoma: emerging insights into the next generation of functional interactions. Neuro Oncol. 2021. 33173943.
Careers
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Novel finding shows T-cells, a central part of the body’s immune response, exhaust sooner in men than in women.
A mechanistic finding for glioblastoma shows mitochondria transfer to tumor cells is common and makes the cancer more aggressive.
Targeting the protein WRD5 could break down the functions of cancer stem cells that allow them to resist treatment.
The research in Dr. Justin Lathia’s lab clarifies SerpinB3’s role in preventing cancer stem cell death, could lead to more effective radiation therapies.
Dr. Lathia has received an eight-year, $5.2 million award from the National Institute of Neurological Disorders and Stroke to further research into the dynamics of immune suppression in malignant brain tumors and target future immune-activating therapies.
Drs. Lathia, Silver and Hine report that a high-fat diet causes hydrogen sulfide dysfunction and leads to more severe disease with poorer outcomes among preclinical glioblastoma models.