# Gregory J. Baker, PhD, PharmD ![GJB](/sites/g/files/omnuum4906/files/styles/hwp_1_1__360x360_scale/public/gregoryjbaker/files/gjb.jpeg?itok=A5yMyd2J) ## **About** Greg obtained his PhD from the University of California, Los Angeles in the laboratory of Drs. Pedro Lowenstein and Maria Castro where he studied mechanisms of glioblastoma (GBM) brain tumor invasion and immune evasion. Prior to this, he received his doctorate in pharmacy (PharmD) from the University of Rhode Island. Greg is now an American Cancer Society Postdoctoral Fellow and Trainee of the Ludwig Center at Harvard Medical School working in the laboratory of Dr. Peter Sorger. His work aims to synthesize an integrated and time-resolved comprehension of GBM’s influence over the cells, cytokines, and network-level architectures of the systemic immune system to ultimately determine whether, and how, immunotherapy can be leveraged against the disease. Since becoming an affliate of the [Laboratory of Systems Pharmacology (LSP)](https://labsyspharm.org/) in the Fall of 2015, Greg has employed mouse models in the development of an extensible *in vivo* screening platform designed to holistically determine how GBM affects host cellular immune organization. Using a 12-color optimized multicolor immunofluorescence panel (OMIP), Greg is able to immunophenotype major mouse leukocyte lineages throughout multiple lymphoid tissues. This approached has allowed him to contextualize and temporally resolve known aspects of GBM immuno-oncology while identifiying novel network-level signatures of tumor-induced immune suppression. His flow-based immunoprofiling strategy has already provided novel insight into how these tumors influence global leukocyte composition; however, an expected transition to cytometry by time-of-flight (CyTOF) as an alternative single-cell analysis technique should dramatically enhance immunoprofiling resolution, allowing Greg to concomitantly measure over 50 cell surface markers and intracellular proteins of interest. Greg is now applying his screening platform to better understand how immunotherapy targeting the PD-1/PD-L1 immune checkpoint axis acts to alleviate tumor-induced immunosuppression in GBM and other solid cancers. Here the platform is being exploited to achieve three goals: (1) identify immune signatures that correlate with response or resistance to therapy, (2) infer mechanisms of drug action, and (3) identify immune cell subsets of novel prognostic value. He next aims to collect both cytokine and mRNA transcript data across multiple immune cell subsets over the course of tumor progression. This information—together with previously collected data on system-wide leukocyte composition—will be used to assemble data-driven, network-level influence diagrams. These diagrams will help guide downstream hypotheses and permit cellular dynamics inferencing. Also on the horizon is the incorporation of genetically-induced tumor models; the study of these systems will allow Greg to interrogate the immunosuppressive influence of clinically-relevant GBM oncogenes. ## Latest News [### Read about our work describing the SYLARAS approach to systemic immunophenotyping. ](/news/preprint-manuscript-describing-our-sylaras-technology-discovery-based) September 23, 2020 description [### Improving Patient Outcomes Bit by Bit: Unraveling the Complexities of Cancer Through the Power of Computation ](/news/improving-patient-outcomes-bit-bit-unraveling-complexities-cancer-through-power) September 18, 2018 Characterized by genetic instability and the capacity to adapt to selective pressure, cancer is one of the most multifaceted, heterogeneous, and intractable human diseases. Despite global efforts to control this life-threatening illness, the majority of... description [ More arrow\_circle\_right ](/news) ## Recent Publications Download 6 citations download- [BibTeX](/bibcite/export?pager_style=no_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=bibtex) - [EndNote X3 XML](/bibcite/export?pager_style=no_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=endnote8) - [EndNote 7 XML](/bibcite/export?pager_style=no_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=endnote7) - [Endnote tagged](/bibcite/export?pager_style=no_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=tagged) - [Marc](/bibcite/export?pager_style=no_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=marc) - [PubMedId](/bibcite/export?pager_style=no_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=pubmed_id) - [RIS](/bibcite/export?pager_style=no_pager&number_of_items=6&sort_field=bibcite_year--desc&taxonomy_filters=&&&format=ris) ### 2023 Iorgulescu JB. [Antigen presentation deficiency, mesenchymal differentiation, and resistance to immunotherapy in the murine syngeneic CT2A tumor model](/publications/antigen-presentation-deficiency-mesenchymal-differentiation-and). Frontiers in Immunology. 2023;13. Iorgulescu JB. [Antigen presentation deficiency, mesenchymal differentiation, and resistance to immunotherapy in the murine syngeneic CT2A tumor model](/publications/antigen-presentation-deficiency-mesenchymal-differentiation-and). Frontiers in Immunology. 2023;13. - add\_circle do\_not\_disturb\_on Abstract - [ descriptionPublisher's Version](https://www.frontiersin.org/articles/10.3389/fimmu.2023.1297932/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Immunology&id=1297932) - [ picture\_as\_pdfiorgulescu\_et\_al.pdf](/sites/g/files/omnuum4906/files/gregoryjbaker/files/iorgulescu_et_al.pdf) **Background:** The GL261 and CT2A syngeneic tumor lines are frequently used as immunocompetent orthotopic mouse models of human glioblastoma (huGBM) but demonstrate distinct differences in their responses to immunotherapy. **Methods:** To decipher the cell... - [ descriptionPublisher's Version](https://www.frontiersin.org/articles/10.3389/fimmu.2023.1297932/full?&utm_source=Email_to_authors_&utm_medium=Email&utm_content=T1_11.5e1_author&utm_campaign=Email_publication&field=&journalName=Frontiers_in_Immunology&id=1297932) - [ picture\_as\_pdfiorgulescu\_et\_al.pdf](/sites/g/files/omnuum4906/files/gregoryjbaker/files/iorgulescu_et_al.pdf) ### 2022 Coy S. [Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma](/publications/single-cell-spatial-analysis-reveals-topology-immunomodulatory-purinergic). Nature Communications. 2022. Coy S. [Single cell spatial analysis reveals the topology of immunomodulatory purinergic signaling in glioblastoma](/publications/single-cell-spatial-analysis-reveals-topology-immunomodulatory-purinergic). Nature Communications. 2022. - add\_circle do\_not\_disturb\_on Abstract - [ descriptionPublisher's Version](https://www.nature.com/articles/s41467-022-32430-w) - [ picture\_as\_pdfcoy\_nat\_comm\_2022.pdf](/sites/g/files/omnuum4906/files/gregoryjbaker/files/coy_nat_comm_2022.pdf) How the glioma immune microenvironment fosters tumorigenesis remains incompletely defined. Here, we use single-cell RNA-sequencing and multiplexed tissue-imaging to characterize the composition, spatial organization, and clinical significance of... - [ descriptionPublisher's Version](https://www.nature.com/articles/s41467-022-32430-w) - [ picture\_as\_pdfcoy\_nat\_comm\_2022.pdf](/sites/g/files/omnuum4906/files/gregoryjbaker/files/coy_nat_comm_2022.pdf) Notarangelo G. [Oncometabolite D-2HG alters T cell metabolism to impair CD8+ T cell function](/publications/oncometabolite-d-2hg-alters-t-cell-metabolism-impair-cd8-t-cell-function). Science. 2022;377(6614):1519–1529. Notarangelo G. [Oncometabolite D-2HG alters T cell metabolism to impair CD8+ T cell function](/publications/oncometabolite-d-2hg-alters-t-cell-metabolism-impair-cd8-t-cell-function). Science. 2022;377(6614):1519–1529. - add\_circle do\_not\_disturb\_on Abstract - [ descriptionPublisher's Version](https://www.science.org/doi/10.1126/science.abj5104) - [ picture\_as\_pdfnotarangelo\_science\_2022....](/sites/g/files/omnuum4906/files/gregoryjbaker/files/notarangelo_science_2022.pdf) Gain-of-function mutations in isocitrate dehydrogenase (IDH) in human cancers result in the production of d-2-hydroxyglutarate (D-2HG), an oncometabolite that promotes tumorigenesis through epigenetic alterations. The cancer cell–intrinsic effects of D... - [ descriptionPublisher's Version](https://www.science.org/doi/10.1126/science.abj5104) - [ picture\_as\_pdfnotarangelo\_science\_2022....](/sites/g/files/omnuum4906/files/gregoryjbaker/files/notarangelo_science_2022.pdf) ### 2021 Schapiro, Sokolov, Yapp. [MCMICRO: A scalable, modular image-processing pipeline for multiplexed tissue imaging](/publications/mcmicro-scalable-modular-image-processing-pipeline-multiplexed-tissue-0). Nature Methods. 2021. Schapiro, Sokolov, Yapp. [MCMICRO: A scalable, modular image-processing pipeline for multiplexed tissue imaging](/publications/mcmicro-scalable-modular-image-processing-pipeline-multiplexed-tissue-0). Nature Methods. 2021. - add\_circle do\_not\_disturb\_on Abstract - [ descriptionPublisher's Version](https://www.nature.com/articles/s41592-021-01308-y) - [ picture\_as\_pdfschapiro\_nat\_methods.pdf](/sites/g/files/omnuum4906/files/gregoryjbaker/files/schapiro_nat_methods.pdf) Highly multiplexed tissue imaging makes detailed molecular analysis of single cells possible in a preserved spatial context. However, reproducible analysis of large multichannel images poses a substantial computational challenge. Here, we describe a... - [ descriptionPublisher's Version](https://www.nature.com/articles/s41592-021-01308-y) - [ picture\_as\_pdfschapiro\_nat\_methods.pdf](/sites/g/files/omnuum4906/files/gregoryjbaker/files/schapiro_nat_methods.pdf) Shah D, Comba A, Faisal SM. [A novel miR1983-TLR7-IFNβ circuit licenses NK cells to kill glioma cells, and is under the control of galectin-1](/publications/novel-mir1983-tlr7-ifn%CE%B2-circuit-licenses-nk-cells-kill-glioma-cells-and). Oncoimmunology. 2021;10(1). Shah D, Comba A, Faisal SM. [A novel miR1983-TLR7-IFNβ circuit licenses NK cells to kill glioma cells, and is under the control of galectin-1](/publications/novel-mir1983-tlr7-ifn%CE%B2-circuit-licenses-nk-cells-kill-glioma-cells-and). Oncoimmunology. 2021;10(1). - add\_circle do\_not\_disturb\_on Abstract - [ descriptionPublisher's Version](https://www.tandfonline.com/doi/full/10.1080/2162402X.2021.1939601) - [ picture\_as\_pdfshah\_oncoimmunology.pdf](/sites/g/files/omnuum4906/files/gregoryjbaker/files/shah_oncoimmunology.pdf) Although pharmacological stimulation of TLRs has anti-tumor effects, it has not been determined whether endogenous stimulation of TLRs can lead to tumor rejection. Herein, we demonstrate the existence of an innate anti-glioma NK-mediated... - [ descriptionPublisher's Version](https://www.tandfonline.com/doi/full/10.1080/2162402X.2021.1939601) - [ picture\_as\_pdfshah\_oncoimmunology.pdf](/sites/g/files/omnuum4906/files/gregoryjbaker/files/shah_oncoimmunology.pdf) ### 2020 Baker G. [SYLARAS: A Platform for the Statistical Analysis and Visual Display of Systemic Immunoprofiling Data and Its Application to Glioblastoma](/publications/sylaras-platform-statistical-analysis-and-visual-display-systemic). Cell Systems. 2020;11(3):272–285. Baker G. [SYLARAS: A Platform for the Statistical Analysis and Visual Display of Systemic Immunoprofiling Data and Its Application to Glioblastoma](/publications/sylaras-platform-statistical-analysis-and-visual-display-systemic). Cell Systems. 2020;11(3):272–285. - add\_circle do\_not\_disturb\_on Abstract - [ descriptionPublisher's Version](https://www.cell.com/cell-systems/fulltext/S2405-4712(20)30285-4) - [ picture\_as\_pdfbaker\_cell\_systems\_2020.p...](/sites/g/files/omnuum4906/files/gregoryjbaker/files/baker_cell_systems_2020.pdf) Accurately profiling systemic immune responses to cancer initiation and progression is necessary for understanding tumor surveillance and, ultimately, improving therapy. Here, we describe the SYLARAS software tool (systemic lymphoid architecture response... - [ descriptionPublisher's Version](https://www.cell.com/cell-systems/fulltext/S2405-4712(20)30285-4) - [ picture\_as\_pdfbaker\_cell\_systems\_2020.p...](/sites/g/files/omnuum4906/files/gregoryjbaker/files/baker_cell_systems_2020.pdf) [ More arrow\_circle\_right ](/publications)