The ECM lab facilitates a Research Experiences and Mentoring (REM) program as a supplement to the NSF EFRI project (EFRI DCheM: Distributed Manufacturing of Personalized Medicines, award #2029139). So far, we have successfully mentored two cohorts of research participants (2022-2023 & 2023-2024). We are currently recruiting research participants for the third year of the REM program, running from May 2024 to May 2025. 

The REM program consists of a 10-week long hands-on research program as well as professional development and mentoring throughout the academic year (May 2024 - May 2025). 

Interested individuals may visit the posting of our open competition NSF REM program on the NSF ETAP website: https://etap.nsf.gov/award/1160/opportunity/8978

We welcome applications from students who have the following backgrounds: LGBTQIA+, minorities, women, economically disadvantaged individuals, veterans, K-12 teachers, and individuals with disabilities. Accepted mentees will receive a stipend, housing, and a meal plan at the U-M campus for the duration of the 10-week hands-on research program. 

REM Program Mission: 

To generate an innovative and diverse future STEM workforce via nurturing research experiences.  

Overall Goal for REM Mentees: 

Mentees are to gain valuable lab experience, develop lab skills, grow their competency in data analysis and interpretation, learn the foundational concepts of biomaterials and drug delivery, and practice research design. 

Mentorship Plan: 

REM mentorship will occur both on and off the U-M campus. 

Recruitment of Mentees: 

We strongly encourage under-represented undergraduate students with no prior hands-on research experience to apply. We highly value a diverse cohort of research participants. 

The effects of the REM program will be observed via long-term updates from mentees on a yearly basis following their completion of the program. 

Descriptions of Research Projects:

1.     Organic Vapor Jet Printing of Anti-fungal Drugs on Degradable Polymer Films for Enhancing Bioavailability.

In this project, the mentee will implement the principles of Organic Vapor Jet Printing (OVJP) in order to alter the microstructure of anti-fungal drugs (such as Griseofulvin, Carbamazepine, Ketoconazole, & Voriconazole) as a function of different printing conditions. As an example, griseofulvin is an antifungal drug which is poorly soluble in aqueous environments. The research participant will print the anti-fungal drugs onto different substrates including glass slides and degradable polymer films such as hydroxypropyl methylcellulose. The printed films will then be used to characterize the crystallinity and particle size of drug molecules via X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). The dissolution tests will be conducted using High Performance Liquid Chromatography (HPLC), and the dissolution rate and solubility of the drug will be quantified in simulated biological fluids. Finally, the mentee will produce OVJPs films of anti-fungal drugs with clinically-relevant drug dosages.

2. Establishing ‘Spring-and-Parachute’ Dissolution for Poorly Soluble Drugs via Organic Vapor Jet Printing (OVJP) without Excipients.

In this project, research participants will optimize OVJP protocols to achieve the spring-and-parachute dissolution phenomenon, wherein a rapid concentration surge of a drug is followed by stabilization at a higher concentration than normally achieved with the typical processing of the drug (with excipients, i.e. inactive ingredients). The newly developed OVJP processing methods will create amorphous, micro-structured drug films that achieve significantly higher dissolution in simulated intestinal fluids without the use of any excipients. The mentee will quantify the microstructural differences, rate of dissolution, recrystallization, and micelle formation via X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), high performance liquid chromatography (HPLC). The data from these experiments will set up new processes for OVJP drug printing that enhance bioavailability and increase efficacy of low solubility BCS - class II drugs. Some of the example drugs to be used in this project include Griseofulvin, Cyclosporine, Azithromycin, Hydroxyzine, or Danazol. 

3.    Printing of Two or More Synergistic Drugs that Target Ovarian Cancers with Organic Vapor Jet Printing (OVJP).

In this project, the research participant will print two or more FDA-approved drugs that work synergistically to kill epithelial ovarian cancer cells. Some examples of such drugs are: atovaquone, talazoparib, paclitaxel, tamoxifen, carbamazepine. The research participant will use OVJP to print the drugs in different patterns on various substrates (i.e. the lid of the cell culture plates) to obtain clinically relevant dosages. The crystallinity, particle size, and dissolution of the printed films will be characterized via X-Ray Diffraction (XRD), Scanning Electron Microscopy (SEM), and High Performance Liquid Chromatography (HPLC). The OVJP printed drug films will then be biologically tested in the 3D spheroids and tumoroids of ovarian cancer cells in collaboration with another research participant and mentor in the ECM (Mehta) Lab.

4.    Effect of Organic Vapor Jet Printed IOVJP) vs. Solvent Dissolved Drugs on the Viability of Epithelial Ovarian Cancer Cells in 3D Spheroids/Tumoroids.

In this project, the research participant will test the efficacy and synergy of two FDA-approved drugs (such as: atovaquone, talazoparib, paclitaxel, tamoxifen, carbamazepine) to kill high grade serous ovarian cancer cells (HGSC). The above mentioned drugs have high permeability and low aqueous solubility, limiting their bioavailability. Mentees will utilize the 384-well hanging drop platform developed in the ECM (Mehta) Lab to generate the 3D spheroids or tumoroids comprised of patient-derived ovarian cancer cell lines that include a chemoresistant isogenic pair. The 3D spheroids will be exposed to either or both drugs of varying dosages, from the OVJP printed films or from solvent dissolved controls. The apoptosis, necrosis and uptake of the drugs will be quantified by the research participant by utilizing microscopy, flow cytometry, and fluorescent functional assays. The results from these experiments will aid to expand understanding of the effect of OVJP on drug bioavailability, which has important implications for preclinical studies and patient care.

5.    Quality Control of Human 3D Tumoroids for Accurate Prediction of Biological Responses to Organic Vapor Jet Printed (OVJP) Drug Films.

As described in some of the previous research projects, we are using an Organic Vapor Jet Printer (OVJP) to print personalized drugs. Therefore, the OVJP printed films will undergo periodic product-testing in order to ensure robust, human biology-centric means of verifying the product quality of the OVJP films. Therefore, the research participant will generate the in vitro 3D tumoroids featuring heterogenous cell types from high grade serous ovarian cancers (HGSC) cell lines. The research participant will conduct bioavailability testing and predict dose-dependent biological responses to drugs in different effective dosages, and characterize the drug delivery kinetics in the 3D patient-derived HGSC tumoroids. The research participant will verify that 3D tumoroids are good assay platforms for quality assurance testing of OVJP printed drug films, and will test them at regular intervals to maintain a high figure of merit (Z' factor, strictly standardized mean difference (SSMD)). They will also compare the drug film efficacy against cancer cells to the toxicity with normal cells, including HFF (fibroblasts), primary human ovarian surface epithelium and primary peripheral blood mononuclear cells (from healthy human volunteers). They will also calculate the occupational hazard limit from the ratio of the IC50 of normal healthy human cells and the HGSC cell lines.

6.    Fallopian Tube Spheroids/Organoids to Study Microenvironment of Early-Stage High-Grade Serous Ovarian Carcinomas (HGSCs).

In this project, the research participant will create physiologically relevant 3D organoids to analyze cell-cell and cell-matrix interactions in the fallopian tube. The secretory epithelial cells in the fimbriae can transform into serous tubular intraepithelial carcinoma (STIC) lesions, that ultimately seed the deadly high-grade serous carcinomas (HGSCs) by detaching from the fallopian tube and spreading to the ovary and peritoneum. The research participant will study the contribution of the non-malignant cell types towards the HGSC progression and metastasis. The research participant will create 3D spheroids/organoids to model the fallopian tube fimbriae using 3 types of cells: fallopian tube secretory epithelial cells (FTSEC), mesenchymal stem cells (MSC), and macrophages (M0) that are stably transduced with a lentivirus to express a unique fluorescent protein, GFP, mCherry, or smURFP, respectively. The presence and viability of each cell type  will be characterized using flow cytometry and confocal microscopy. Moreover, the 3D organoids will be utilized to compare the impact of drug treatments developed in other projects mentioned above. By understanding the cellular dynamics within the HGSC precursor microenvironment, we hope to contribute to advancements in ovarian cancer treatment and patient outcomes.

7.    Mathematical Simulation of Drug Co-crystallization.

Co-crystallization of drug and conformers is utilized to improve solubility and stabilize the physicochemical properties of the drug. In this project, the research participant will develop molecular simulations of co-crystal formation, crystal nucleation, structure and dynamics, and dissolution. The mentee will develop methods of molecular dynamics simulations of co-crystal growth from the vapor phase. The research participant will also determine the temperature dependence of the growth rate of co-crystals from the vapor phase, using course-grained force field for MD simulations. These simulations will also determine the crystal lattice energy, molecule attachment energy, relative growth rates of facets, as well as dissolution rates in solvent. 

8.  Development of an In Vitro Fallopian Tube Epithelial Cell Model to Study HGSC Initiation

This project focuses on constructing an in vitro model of fallopian tube epithelial cells to investigate the origins of high-grade serous ovarian carcinoma (HGSC), which often arises from the secretory cells in the fimbria. Since HGSC is characterized by the proliferation of secretory cells and loss of ciliated cells, our model aims to recreate these early events to better understand tumor initiation and progression. In this project, the mentee will collaborate with a PhD candidate, utilizing tissue engineering and cellular biology techniques to isolate and culture fallopian tube epithelial cells. The model will enable studies of the cellular and molecular changes leading to HGSC, potentially revealing early-detection biomarkers and therapeutic targets. The project is positioned to significantly impact our understanding of the early stages of HGSC by enabling detailed studies of the initiation events at a cellular level. The mentee’s responsibilities will include aseptic mammalian cell culture, 3D model development, genetic modification, cell-type characterization, and assessment of responses. Outcomes will enhance our grasp of HGSC's onset and offer the mentee substantial research experience in a clinically-relevant field.