Julie Schwarz, M.D., Ph.D.

Professor and Vice Chair of Research
Radiation Oncology
Cancer Biology
Cell Biology and Physiology

Cancer Biology Program
Molecular Cell Biology Program

  • 314-273-0275

  • 314-362-6869

  • 314-747-5498

  • 4511 Forest Park, 3rd floor

  • jschwarz@wustl.edu

  • https://schwarzlab.wustl.edu/

  • @JulieSchwarz14

  • Tumor metabolism, glycolysis, glutaminolysis, imaging, microenvironment, HPV, immunology, radiation therapy

  • Studying cancer therapy resistance mechanisms in humans and preclinical models

Research Abstract:

We use well annotated clinical databases paired with prospectively collected patient tumor banks and state of the art sequencing technologies to perform high quality translational research in gynecologic cancers. At Washington University we maintain one the largest tumor repositories for cervical cancer, which includes well annotated specimens collected before and during chemoradiation treatment. We are currently using this repository to test the influence of Human Papilloma Virus (HPV) genotype and gene expression on cervical cancer outcomes, characterize the biology of HPV negative cervical tumors, and identify novel mutations associated with local recurrence and distant metastasis after treatment. We take these observations, derived directly from patient data, to the bench to conceptualize, optimize and test novel drug and radiotherapy combinations, which are then moved forward in the context of investigator-initiated clinical trials.

The majority of the work done to date in the lab has focused on tumor metabolism, specifically increased rates of glucose uptake and glycolysis and the association between this metabolic phenotype and resistance to cancer treatment. We have had a long standing interest in the association between tumor glucose metabolism and radiation therapy resistance. This work has included clinical studies with 18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET) scans as well as preclinical studies performed in cancer cell lines and mouse tumor models, including patient derived xenografts and genetically engineered mouse models. We have used this approach to develop metabolic strategies that increase tumor oxidative stress and can be used to increase radiation sensitivity in treatment-resistant tumors. More recently, we have been developing new strategies that target tumor dependence on alternative carbon sources including glutamine and free fatty acids.

Our work has now expanded to include the role of tumor microenvironment, and specifically the tumor immune microenvironment, in mediating cancer therapy resistance. This work includes active research collaborations with other laboratories studying other tumor types (such as sarcoma and pancreatic cancer). Using 2D and 3D co-culture systems, we are studying how tumor cells and immune cells in microenvironment share (and compete for) nutrients and how this process impacts anti-tumor immunity.

Current projects include:
1) Using single cell sequencing approaches to study treatment effects on tumor cells and the tumor microenvironment
2) Glucose and glutamine metabolism as targets for cancer therapy
3) Treatment related changes in tumor fat metabolism
4) Targeting myeloid derived cells as a mechanism to improve anti-tumor immunity

Mentorship and Commitment to Diversity Statement:
As a mentor, I am deeply committed to the personal and professional development of all trainees. I have a strong track record of mentorship of trainees at all levels including undergraduates, graduate students, medical students, MSTP students, residents, fellows and post doctoral researchers. My priorities as a mentor are to work with each trainee to identify career goals, develop and execute a plan to build towards those goals then advise during post training interviews and negotiations. My lab's research environment is highly collaborative, active and supportive. We are committed to improving diversity, equity, inclusion and accountability in the research sciences. We do this by supporting trainees of all backgrounds, actively promoting their career choices and advancement (even after they graduate from the lab!) and by studying the biology of cancers that affect underserved populations. Keys to success thus far for trainees in my lab have been performing the very highest quality science with enthusiasm and mastering scientific communication including written and oral communication. The primary key, however, is finding passion and joy in what you do everyday! As a mother of two, married to another scientist (Brian Edelson - check out his dbbs page!) we believe in and actively cultivate work life balance.

Selected Publications:

1. Ruiz FJ, Inkman M, Rashmi R, Muhammad N, Gabriel N, Miller CA, McLellan MD, Goldstein M, Markovina S, Grigsby PW, Zhang J, Schwarz JK. HPV transcript expression affects cervical cancer response to chemoradiation. JCI Insight. 2021 Jul 13:138734. doi: 10.1172/jci.insight.138734. Online ahead of print

2. Floberg, JM, Zhang J, Muhammad N, DeWees TA, Inkman M, Chen K, Lin AJ, Rashmi R, Jayachandran K, Edelson BT, Siegel BA, Dehdashti F, Grigsby PW, Markovina S, Schwarz JK. Standardized uptake value for 18F-fluorodeoxyglucose is a marker of inflammatory state and immune infiltrate in cervical cancer. Clin Cancer Res, 2021 Apr 2021 Apr 5. doi: 10.1158/1078-0432.CCR-20-4450. PMID: 33820781 *article selected for journal highlight

3. Zhang J, Rashmi R, Inkman M, Jayachandran K, Ruiz F, Waters MR, Grigsby PW, Markovina S, Schwarz JK. Integrating imaging and RNASeq improves outcome prediction in cervical cancer. J Clin Invest. 2021 Mar 1;131(5):e139232. doi: 10.1172/JCI139232. PMID: 33645544

4. Rashmi R, Jayachandran K, Zhang J, Menon V, Muhammad N, Zahner M, Ruiz F, Zhang S, Cho K, Wang Y, Huang X, Huang Y, McCormick ML, Rogers BE, Spitz DR, Patti GJ, Schwarz JK. Glutaminase inhibitors induce thiol-mediated oxidative stress and radio-sensitization in treatment resistance cervical cancers. Mol Cancer Ther. 2020 Oct 21:molcanther.0271.2020.doi: 10.1158/1535-7163.MCT-20-0271. Online ahead of print. PMID: 33087507. *article selected for journal highlight

5. Hegde S, Krisnawan VE, Herzog BH, Zuo C, Breden MA, Knolhoff BL, Hogg GD, Tang JP, Baer JM, Mpoy C, Lee KB, Alexander KA, Rogers BE, Murphy KM, Hawkkins WG, Fields RC, DeSelm CJ, Schwarz JK, DeNardo DG. Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer. Cancer Cell. 2020 Mar 16;37(3):289-307.e9. doi: 10.1016/j.ccell.2020.02.08. PMID: 32183949. PubMed Central PMCID: PMC7181337

6. Floberg JM, Wang L, Bandara N, Rashmi R, Mpoy C, Garbow J, Rogers BE, Patti GJ, Schwarz JK. Alteration of cellular reduction potential will change 64Cu-ATSM signal with or without hypoxia . J Nucl Med 2020 Mar;61(3):427-432. Oct 4. doi: 10.2967/jnumed.119.230805. 2019 Oct 4. PMID: 31586008. PubMed Central PMCID: PMC7067520

7. Wisdom AJ, Hong CS, Lin AJ, Cooper DE, Zhang J, Xu ES, Kuo H-C, Mowery YM, Carpenter DJ, Kadakia K, Himes JE, Luo L, Ma Y, Williams N, Cardona DM, Haldar M, Diao Y, Markovina S, Schwarz JK and DG Kirsch. Neutrophils promote resistance to radiation therapy. Proc Natl Acad Sci USA. 2019 Sep 10;116(37):18584-18589. doi: 10.1073/pnas.1901562116. Epub 2019 Aug 28. PMID: 31462499; Pub Med Central PMCID: PMC6744874.

8. Panni RZ, Herndon JM, Zuo C, Hegde S, Hogg GD, Knolhoff BL, Breden MA, Li X, Krisnawan VE, Khan SQ, Schwarz JK, Rogers BE, Fields RC, Hawkins WG, Gupta V, DeNardo DG. Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies. Sci Transl Med. 2019 Jul 3;11(499). pii: eaau9240. doi: 10.1126/scitranslmed.aau9240 PMID 31270275. PubMed Central PMCID: PMC7197026.

9. Rashmi R, Huang X, Floberg, JM, Elhammali, A, McCormick, ML, Patti, GJ, Spitz, DR and JK Schwarz. Radio-resistant cervical cancers are sensitive to inhibition of glycolysis and redox metabolism. Cancer Res 2018 Mar 15;78(6):1392-1403.

Last Updated: 8/18/2021 7:36:02 AM

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