University Of Miami School Of Medicine
United States
A comprehensive liquid biopsy platform for detection and prognostication in early stage breast cancer
We seek to develop robust platforms for capturing, enumerating and analyzing circulating tumor cells and associated cancer cells from the blood of cancer patients. We will leverage our previously developed precisely engineered microfilter platform that allows effective separation and collection of viable CTC from patient blood. In parallel, we have developed novel imaging methods perfectly suited for rapid analyses for circulating tumor cells, clusters and associated cancer cell subtypes (such as Cancer Associated Fibroblasts, or CAF). We propose to integrate these two novel technologies to create a robust diagnostic tool for clinical pathology as well as basic research that enables capture, enumeration, and analyses of circulating tumor cells and associated cancer cells. Our multidisciplinary team proposes the following Specific Aims: 1) Build and validate the technology to rapidly acquire CTC/CAF images using Fourier Ptychographic Microscopy and evaluate the images with a deep learning algorithm 2) Evaluation of the integrated platform for using CTC/CAF in predicting recurrence/survival in early stage breast cancer patients For these studies in early stage breast cancer, we have robust collaborations with industry partners in Circulogix Inc (Microfilter technology for cell capture), ClearBridge Inc. (FPM imaging of the microfilter surface), and Google Software (Deep learning algorithm for analyzing FPM images of microfilter). The ability to reliably and rapidly detect and analyze CTC and associated cancer cells in early stage breast cancer patients would deliver a major new tool for oncology research, a platform for screening of novel drugs, and a critical advance in precision cancer management.
Publications
- Alver CG, Drabbe E, Ishahak M, Agarwal A. Roadblocks confronting widespread dissemination and deployment of Organs on Chips. Nature communications. 2024 Jun 15;15(1):5118. PMID: 38879554
- Buchwald P, Cechin SR, Weaver JD, Stabler CL. Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets. Biomedical engineering online. 2015 Mar 28;14:28. PMID: 25889474
- Lin SS, Zhou H, Cote RJ, Watson M, Govindan R, Yang C. Impact of Stain Variation and Color Normalization for Prognostic Predictions in Pathology. ArXiv. 2024 Sep 12. PMID: 39314500
- Besser RR, Bowles AC, Alassaf A, Carbonero D, Maciel R, Saporta M, Agarwal A. A Chemically Defined Common Medium for Culture of C2C12 Skeletal Muscle and Human Induced Pluripotent Stem Cell Derived Spinal Spheroids. Cellular and molecular bioengineering. 2020 Jun 10;13(6):605-619. doi: 10.1007/s12195-020-00624-1. eCollection 2020 Dec. PMID: 33281990
- Garcia-Contreras M, Tamayo-Garcia A, Pappan KL, Michelotti GA, Stabler CL, Ricordi C, Buchwald P. Metabolomics Study of the Effects of Inflammation, Hypoxia, and High Glucose on Isolated Human Pancreatic Islets. Journal of proteome research. 2017 Jun 2;16(6):2294-2306. Epub 2017 May 9. PMID: 28452488
- Yang YP, Giret TM, Cote RJ. Circulating Tumor Cells from Enumeration to Analysis: Current Challenges and Future Opportunities. Cancers. 2021 May 31;13. (11). PMID: 34072844
- Liang M, Yang C. Implementation of free-space Fourier Ptychography with near maximum system numerical aperture. Optics express. 2022 Jun 6;30(12):20321-20332. PMID: 36224781
- Lin S, Zhou H, Watson M, Govindan R, Cote RJ, Yang C. Impact of stain variation and color normalization for prognostic predictions in pathology. Scientific reports. 2025 Jan 18;15(1):2369. PMID: 39827151
- Wang G, Black PC, Goebell PJ, Ji L, Cordon-Cardo C, Schmitz-Dräger B, Hawes D, Czerniak B, Minner S, Sauter G, Waldman F, Groshen S, Cote RJ, Dinney CP. Prognostic markers in pT3 bladder cancer: A study from the international bladder cancer tissue microarray project. Urologic oncology. 2021 May;39(5):301.e17-301.e28. Epub 2021 Feb 7. PMID: 33563539
- Menegaz D, Hagan DW, Almaça J, Cianciaruso C, Rodriguez-Diaz R, Molina J, Dolan RM, Becker MW, Schwalie PC, Nano R, Lebreton F, Kang C, Sah R, Gaisano HY, Berggren PO, Baekkeskov S, Caicedo A, Phelps EA. Mechanism and effects of pulsatile GABA secretion from cytosolic pools in the human beta cell. Nature metabolism. 2019 Nov;1(11):1110-1126. Epub 2019 Nov 15. PMID: 32432213
- Jiang K, Chaimov D, Patel SN, Liang JP, Wiggins SC, Samojlik MM, Rubiano A, Simmons CS, Stabler CL. 3-D physiomimetic extracellular matrix hydrogels provide a supportive microenvironment for rodent and human islet culture. Biomaterials. 2019 Apr;198:37-48. Epub 2018 Sep 7. PMID: 30224090
- Buchwald P, Tamayo-Garcia A, Manzoli V, Tomei AA, Stabler CL. Glucose-stimulated insulin release: Parallel perifusion studies of free and hydrogel encapsulated human pancreatic islets. Biotechnology and bioengineering. 2018 Jan;115(1):232-245. Epub 2017 Sep 19. PMID: 28865118
- Alcazar O, Buchwald P. Concentration-Dependency and Time Profile of Insulin Secretion: Dynamic Perifusion Studies With Human and Murine Islets. Frontiers in endocrinology. 2019 Oct 2;10:680. doi: 10.3389/fendo.2019.00680. eCollection 2019. PMID: 31632354
- Besser RR, Bowles AC, Alassaf A, Carbonero D, Claure I, Jones E, Reda J, Wubker L, Batchelor W, Ziebarth N, Silvera R, Khan A, Maciel R, Saporta M, Agarwal A. Enzymatically crosslinked gelatin-laminin hydrogels for applications in neuromuscular tissue engineering. Biomaterials science. 2020 Jan 21;8(2):591-606. PMID: 31859298
- Yang EY, Kronenfeld JP, Stabler CL. Engineering biomimetic materials for islet transplantation. Current diabetes reviews. 2015;11(3):163-9. PMID: 25776871
- Shen C, Rawal S, Brown R, Zhou H, Agarwal A, Watson MA, Cote RJ, Yang C. Automatic detection of circulating tumor cells and cancer associated fibroblasts using deep learning. Scientific reports. 2023 Apr 7;13(1):5708. PMID: 37029224
- Liang M, Bernadt C, Wong SBJ, Choi C, Cote R, Yang C. All-in-focus fine needle aspiration biopsy imaging based on Fourier ptychographic microscopy. Journal of pathology informatics. 2022 Jun 30;13:100119. doi: 10.1016/j.jpi.2022.100119. eCollection 2022. PMID: 36268073
- Mayo V, Bowles AC, Wubker LE, Ortiz I, Cordoves AM, Cote RJ, Correa D, Agarwal A. Human-derived osteoblast-like cells and pericyte-like cells induce distinct metastatic phenotypes in primary breast cancer cells. Experimental biology and medicine (Maywood, N.J.). 2021 Apr;246(8):971-985. Epub 2020 Nov 19. PMID: 33210551
- Zhou H, Watson M, Bernadt CT, Lin SS, Lin CY, Ritter JH, Wein A, Mahler S, Rawal S, Govindan R, Yang C, Cote RJ. AI-guided histopathology predicts brain metastasis in lung cancer patients. The Journal of pathology. 2024 May;263(1):89-98. Epub 2024 Mar 4. PMID: 38433721
- Zhou H, Lin S, Watson M, Bernadt CT, Zhang O, Liao L, Govindan R, Cote RJ, Yang C. Length-scale study in deep learning prediction for non-small cell lung cancer brain metastasis. Scientific reports. 2024 Sep 27;14(1):22328. PMID: 39333630