Education & Certifications

  • Doctor of Philosophy, Duke University (2021)
  • Bachelor of Science, Baylor University (2016)
  • PhD, Duke University, Biomedical Engineering (2021)
  • BS, Baylor University, General Engineering - Concentration in Biomedical Applications (2016)


  • Corrine Nief. "United States Patent US10278806B2 Ureteral stent and method", Baylor University, Jan 1, 2017

Current Research and Scholarly Interests

I'm interested in developing novel diagnostics and therapeutics for cancer patients using my background in computational biology and engineering. I'm specifically interested in women's cancers and the role of the tumor-immune microenvironment, metabolism, and hormonal interactions.

During my PhD, under Dr. Nimmi Ramanujam, I developed a low-cost tumor ablation method for breast and cervical cancer to increase access to care in low-resource settings. My method consisted of injecting cytotoxic ethanol along with a phase changing polymer directly in to tumors. I found that this method was able to deliver ethanol soluble small molecules (i.e. cyclophosphamide) directly into the tumor in a slow releasing depot and produce a systemic anti-tumor immunophenotype in triple-negative breast cancer models.

Currently I'm working with Dr. Brooke Howitt and Dr. Andrew Gentles, using machine learning to identify RNA signatures of recurrent endometrioid endometrial cancer with the hopes of identifying markers of aggressive disease.

All Publications

  • Endometrioid Endometrial RNA Index Predicts Recurrence in Stage I Patients. Clinical cancer research : an official journal of the American Association for Cancer Research Nief, C. A., Hammer, P. M., Wang, A., Charu, V., Tanweer, A., Litkouhi, B., Kidd, E., Gentles, A. J., Howitt, B. E. 2024


    PURPOSE: Risk prediction with genomic and transcriptomic data has the potential to improve patient outcomes by enabling clinicians to identify patients requiring adjuvant treatment approaches, while sparing low-risk patients from unnecessary interventions. Endometrioid endometrial carcinoma (EEC) is the most common cancer in women in developed countries, and rates of endometrial cancer are increasing.EXPERIMENTAL DESIGN: We collected a 105-patient case-control cohort of stage I EEC comprised of 45 patients who experienced recurrence less than 6 years after excision, and 60 FIGO grade matched controls without recurrence. We first utilized two RNA based, previously validated machine learning approaches, namely EcoTyper and Complexity Index in Sarcoma (CINSARC). We developed Endometrioid Endometrial RNA Index (EERI) which uses RNA expression data from 46 genes to generate a personalized risk score for each patient. EERI was trained on our 105-patient cohort and tested on a publicly available cohort of 263 stage I EEC patients.RESULTS: EERI was able to predict recurrences with 94% accuracy in the training set and 81% accuracy in the test set. In the test set, patients assigned as EERI high-risk were significantly more likely to experience recurrence (30%) than the EERI low-risk group (1%) with a hazard ratio of 9.9 (95% CI 4.1-23.8, P <0.001).CONCLUSIONS: Tumors with high-risk genetic features may require additional treatment or closer monitoring and are not readily identified using traditional clinicopathologic and molecular features. EERI performs with high sensitivity and modest specificity, which may benefit from further optimization and validation in larger independent cohorts.

    View details for DOI 10.1158/1078-0432.CCR-23-3158

    View details for PubMedID 38669067

  • Polarization of Endothelial and Epithelial Cell States Predicts Recurrence in Endometrial Endometrioid Carcinoma Nief, C., Hammer, P., Wang, A., Gentles, A., Howitt, B. ELSEVIER SCIENCE INC. 2023: S962-S963
  • Regression of Malignant Pleural Mesothelioma in Absence of Chemotherapy or Surgery: A Case Series. Clinical lung cancer Nief, C. A., No, H. J., Louie, C. Y., Vitzthum, L., Das, M. 2022

    View details for DOI 10.1016/j.cllc.2022.10.002

    View details for PubMedID 36323592

  • Ethanol Ablation Therapy Drives Immune-Mediated Antitumor Effects in Murine Breast Cancer Models. Cancers Nief, C. A., Swartz, A. M., Chelales, E., Sheu, L. Y., Crouch, B. T., Ramanujam, N., Nair, S. K. 2022; 14 (19)


    Ethanol ablation is a minimally invasive, cost-effective method of destroying tumor tissue through an intratumoral injection of high concentrations of cytotoxic alcohol. Ethyl-cellulose ethanol (ECE) ablation, a modified version of ethanol ablation, contains the phase-changing polysaccharide ethyl-cellulose to reduce ethanol leakage away from the tumor. Ablation produces tissue necrosis and initiates a wound healing process; however, the characteristic of the immunologic events after ECE ablation of tumors has yet to be explored. Models of triple-negative breast cancer (TNBC), which are classically immunosuppressive and difficult to treat clinically, were used to characterize the immunophenotypic changes after ECE ablation. In poorly invasive TNBC rodent models, the injury to the tumor induced by ECE increased tumor infiltrating lymphocytes (TILs) and reduced tumor growth. In a metastatic TNBC model (4T1), TILs did not increase after ECE ablation, though lung metastases were reduced. 4T1 tumors secrete high levels of granulocytic colony stimulating factor (G-CSF), which induces a suppressive milieu of granulocytic myeloid-derived suppressor cells (gMDSCs) aiding in the formation of metastases and suppression of antitumor immunity. We found that a single intratumoral injection of ECE normalized tumor-induced myeloid changes: reducing serum G-CSF and gMDSC populations. ECE also dampened the suppressive strength of gMDSC on CD4 and CD8 cell proliferation, which are crucial for anti-tumor immunity. To demonstrate the utility of these findings, ECE ablation was administered before checkpoint inhibitor (CPI) therapy in the 4T1 model and was found to significantly increase survival compared to a control of saline and CPI. Sixty days after tumor implant no primary tumors or metastatic lung lesions were found in 6/10 mice treated with CPI plus ECE, compared to 1/10 with ECE alone and 0/10 with CPI and saline.

    View details for DOI 10.3390/cancers14194669

    View details for PubMedID 36230591

  • Targeting Tumor Acidosis and Regulatory T Cells Unmasks Anti-Metastatic Potential of Local Tumor Ablation in Triple-Negative Breast Cancer. International journal of molecular sciences Nief, C. A., Gonzales, A., Chelales, E., Agudogo, J. S., Crouch, B. T., Nair, S. K., Ramanujam, N. 2022; 23 (15)


    Triple-negative breast cancer (TNBC) is an immunologically heterogenous disease that lacks clinically actionable targets and is more likely to progress to metastatic disease than other types of breast cancer. Tumor ablation has been used to increase response rates to checkpoint inhibitors, which remain low for TNBC patients. We hypothesized that tumor ablation could produce an anti-tumor response without using checkpoint inhibitors if immunosuppression (i.e., Tregs, tumor acidosis) was subdued. Tumors were primed with sodium bicarbonate (200 mM p.o.) to reduce tumor acidosis and low-dose cyclophosphamide (100-200 mg/kg i.p.) to deplete regulatory T cells, as has been shown independently in previous studies. A novel injectable ablative was then used to necrose the tumor, release tumor antigens, and initiate an immune event that could create an abscopal effect. This combination of bicarbonate, cyclophosphamide, and ablation, called "BiCyclA", was tested in three syngeneic models of TNBC: E0771 (C57BL/6), 67NR (BALB/c), and 4T1-Luc (BALB/c). In E0771 and 67NR, BiCyclA therapy significantly reduced tumor growth and cured 5/7 and 6/10 mice 50 days after treatment respectively. In the metastatic 4T1-Luc tumors, for which surgery and checkpoint inhibitors fail, BiCyclA cured 5/10 mice of primary tumors and lung metastases. Notably, CD4+ and CD8+ T cells were found to be crucial for the anti-metastatic response, and cured mice were able to resist tumor rechallenge, suggesting production of immune memory. Reduction of tumor acidity and regulatory T cells with ablation is a simple yet effective therapy for local and systemic tumor control with broad applicability as it is not limited by expensive supplies.

    View details for DOI 10.3390/ijms23158479

    View details for PubMedID 35955613

  • Radiologic-pathologic analysis of increased ethanol localization and ablative extent achieved by ethyl cellulose. Scientific reports Chelales, E., Morhard, R., Nief, C., Crouch, B., Everitt, J. I., Sag, A. A., Ramanujam, N. 2021; 11 (1): 20700


    Ethanol provides a rapid, low-cost ablative solution for liver tumors with a small technological footprint but suffers from uncontrolled diffusion in target tissue, limiting treatment precision and accuracy. Incorporating the gel-forming polymer ethyl cellulose to ethanol localizes the distribution. The purpose of this study was to establish a non-invasive methodology based on CT imaging to quantitatively determine the relationship between the delivery parameters of the EC-ethanol formulation, its distribution, and the corresponding necrotic volume. The relationship of radiodensity to ethanol concentration was characterized with water-ethanol surrogates. Ex vivo EC-ethanol ablations were performed to optimize the formulation (n = 6). In vivo ablations were performed to compare the optimal EC-ethanol formulation to pure ethanol (n = 6). Ablations were monitored with CT and ethanol distribution volume was quantified. Livers were removed, sectioned and stained with NADH-diaphorase to determine the ablative extent, and a detailed time-course histological study was performed to assess the wound healing process. CT imaging of ethanol-water surrogates demonstrated the ethanol concentration-radiodensity relationship is approximately linear. A concentration of 12% EC in ethanol created the largest distribution volume, more than eight-fold that of pure ethanol, ex vivo. In vivo, 12% EC-ethanol was superior to pure ethanol, yielding a distribution volume three-fold greater and an ablation zone six-fold greater than pure ethanol. Finally, a time course histological evaluation of the liver post-ablation with 12% EC-ethanol and pure ethanol revealed that while both induce coagulative necrosis and similar tissue responses at 1-4 weeks post-ablation, 12% EC-ethanol yielded a larger ablation zone. The current study demonstrates the suitability of CT imaging to determine distribution volume and concentration of ethanol in tissue. The distribution volume of EC-ethanol is nearly equivalent to the resultant necrotic volume and increases distribution and necrosis compared to pure ethanol.

    View details for DOI 10.1038/s41598-021-99985-4

    View details for PubMedID 34667252

    View details for PubMedCentralID PMC8526742

  • Optimizing ethyl cellulose-ethanol delivery towards enabling ablation of cervical dysplasia. Scientific reports Mueller, J. L., Morhard, R., DeSoto, M., Chelales, E., Yang, J., Nief, C., Crouch, B., Everitt, J., Previs, R., Katz, D., Ramanujam, N. 2021; 11 (1): 16869


    In low-income countries, up to 80% of women diagnosed with cervical dysplasia do not return for follow-up care, primarily due to treatment being inaccessible. Here, we describe development of a low-cost, portable treatment suitable for such settings. It is based on injection of ethyl cellulose (EC)-ethanol to ablate the transformation zone around the os, the site most impacted by dysplasia. EC is a polymer that sequesters the ethanol within a prescribed volume when injected into tissue, and this is modulated by the injected volume and delivery parameters (needle gauge, bevel orientation, insertion rate, depth, and infusion rate). Salient injection-based delivery parameters were varied in excised swine cervices. The resulting injection distribution volume was imaged with a wide-field fluorescence imaging device or computed tomography. A 27G needle and insertion rate of 10 mm/s achieved the desired insertion depth in tissue. Orienting the needle bevel towards the outer edge of the cervix and keeping infusion volumes ≤ 500 µL minimized leakage into off-target tissue. These results guided development of a custom hand-held injector, which was used to locate and ablate the upper quadrant of a swine cervix in vivo with no adverse events or changes in host temperature or heart rate. After 24 h, a distinct region of necrosis was detected that covered a majority (> 75%) of the upper quadrant of the cervix, indicating four injections could effectively cover the full cervix. The work here informs follow up large animal in vivo studies, e.g. in swine, to further assess safety and efficacy of EC-ethanol ablation in the cervix.

    View details for DOI 10.1038/s41598-021-96223-9

    View details for PubMedID 34413378

    View details for PubMedCentralID PMC8376953

  • Polymer-assisted intratumoral delivery of ethanol: Preclinical investigation of safety and efficacy in a murine breast cancer model. PloS one Nief, C., Morhard, R., Chelales, E., Adrianzen Alvarez, D., Bourla Bs, I., Lam, C. T., Sag, A. A., Crouch, B. T., Mueller, J. L., Katz, D., Dewhirst, M. W., Everitt, J. I., Ramanujam, N. 2021; 16 (1): e0234535


    Focal tumor ablation with ethanol could provide benefits in low-resource settings because of its low overall cost, minimal imaging technology requirements, and acceptable clinical outcomes. Unfortunately, ethanol ablation is not commonly utilized because of a lack of predictability of the ablation zone, caused by inefficient retention of ethanol at the injection site. To create a predictable zone of ablation, we have developed a polymer-assisted ablation method using ethyl cellulose (EC) mixed with ethanol. EC is ethanol-soluble and water-insoluble, allowing for EC-ethanol to be injected as a liquid and precipitate into a solid, occluding the leakage of ethanol upon contact with tissue. The aims of this study were to compare the 1) safety, 2) release kinetics, 3) spatial distribution, 4) necrotic volume, and 5) overall survival of EC-ethanol to conventional ethanol ablation in a murine breast tumor model. Non-target tissue damage was monitored through localized adverse events recording, ethanol release kinetics with Raman spectroscopy, injectate distribution with in vivo imaging, target-tissue necrosis with NADH-diaphorase staining, and overall survival by proxy of tumor growth. EC-ethanol exhibited decreased localized adverse events, a slowing of the release rate of ethanol, more compact injection zones, 5-fold increase in target-tissue necrosis, and longer overall survival rates compared to the same volume of pure ethanol. A single 150 μL dose of 6% EC-ethanol achieved a similar survival probability rates to six daily 50 μL doses of pure ethanol used to simulate a slow-release of ethanol over 6 days. Taken together, these results demonstrate that EC-ethanol is safer and more effective than ethanol alone for ablating tumors.

    View details for DOI 10.1371/journal.pone.0234535

    View details for PubMedID 33507942

    View details for PubMedCentralID PMC7843014

  • Understanding Factors Governing Distribution Volume of Ethyl Cellulose-Ethanol to Optimize Ablative Therapy in the Liver. IEEE transactions on bio-medical engineering Morhard, R., Mueller, J. L., Tang, Q., Nief, C., Chelales, E., Lam, C. T., Alvarez, D. A., Rubinstein, M., Katz, D. F., Ramanujam, N. 2020; 67 (8): 2337-2348


    Ethanol ablation, the injection of ethanol to induce necrosis, was originally used to treat hepatocellular carcinoma, with survival rates comparable to surgery. However, efficacy is limited due to leakage into surrounding tissue. To reduce leakage, we previously reported incorporating ethyl cellulose (EC) with ethanol as this mixture forms a gel when injected into tissue. To further develop EC-ethanol injection as an ablative therapy, the present study evaluates the extent to which salient injection parameters govern the injected fluid distribution.Utilizing ex vivo swine liver, injection parameters (infusion rate, EC%, infusion volume) were examined with fluorescein added to each solution. After injection, tissue samples were frozen, sectioned, and imaged.While leakage was higher for ethanol and 3%EC-ethanol at a rate of 10 mL/hr compared to 1 mL/hr, leakage remained low for 6%EC-ethanol regardless of infusion rate. The impact of infusion volume and pressure were also investigated first in tissue-mimicking surrogates and then in tissue. Results indicated that there is a critical infusion pressure beyond which crack formation occurs leading to fluid leakage. At a rate of 10 mL/hr, a volume of 50 μL remained below the critical pressure.Although increasing the infusion rate increases stress on the tissue and the risk of crack formation, injections of 6%EC-ethanol were localized regardless of infusion rate. To further limit leakage, multiple low-volume infusions may be employed.These results, and the experimental framework developed to obtain them, can inform optimizing EC-ethanol to treat a range of medical conditions.

    View details for DOI 10.1109/TBME.2019.2960049

    View details for PubMedID 31841399

    View details for PubMedCentralID PMC7295656

  • Development of enhanced ethanol ablation as an alternative to surgery in treatment of superficial solid tumors. Scientific reports Morhard, R., Nief, C., Barrero Castedo, C., Hu, F., Madonna, M., Mueller, J. L., Dewhirst, M. W., Katz, D. F., Ramanujam, N. 2017; 7 (1): 8750


    While surgery is at the foundation of cancer treatment, its access is limited in low-income countries. Here, we describe development of a low-cost alternative therapy based on intratumoral ethanol injection suitable for resource-limited settings. Although ethanol-based tumor ablation is successful in treating hepatocellular carcinomas, the necessity for multiple treatments, injection of large fluid volumes, and decreased efficacy in treatment of non-capsulated tumors limit its applicability. To address these limitations, we investigated an enhanced ethanol ablation strategy to retain ethanol within the tumor through the addition of ethyl cellulose. This increases the viscosity of injected ethanol and forms an ethanol-based gel-phase upon exposure to the aqueous tumor environment. This technique was first optimized to maximize distribution volume, using tissue-simulating phantoms. Then, chemically-induced epithelial tumors in the hamster cheek pouch were treated. As controls, pure ethanol injections of either four times or one-fourth the tumor volume induced complete regression of 33% and 0% of tumors, respectively. In contrast, ethyl cellulose-ethanol injections of one-fourth the tumor volume induced complete regression in 100% of tumors. These results contribute to proof-of-concept for enhanced ethanol ablation as a novel and effective alternative to surgery for tumor treatment, with relevance to resource-limited settings.

    View details for DOI 10.1038/s41598-017-09371-2

    View details for PubMedID 28821832

    View details for PubMedCentralID PMC5562881

  • Atomistic simulations indicate the c-subunit ring of the F1Fo ATP synthase is not the mitochondrial permeability transition pore. eLife Zhou, W., Marinelli, F., Nief, C., Faraldo-Gómez, J. D. 2017; 6


    Pathological metabolic conditions such as ischemia induce the rupture of the mitochondrial envelope and the release of pro-apoptotic proteins, leading to cell death. At the onset of this process, the inner mitochondrial membrane becomes depolarized and permeable to osmolytes, proposedly due to the opening of a non-selective protein channel of unknown molecular identity. A recent study purports that this channel, referred to as Mitochondrial Permeability Transition Pore (MPTP), is formed within the c-subunit ring of the ATP synthase, upon its dissociation from the catalytic domain of the enzyme. Here, we examine this claim for two c-rings of different lumen width, through calculations of their ion conductance and selectivity based on all-atom molecular dynamics simulations. We also quantify the likelihood that the lumen of these c-rings is in a hydrated, potentially conducting state rather than empty or blocked by lipid molecules. These calculations demonstrate that the structure and biophysical properties of a correctly assembled c-ring are inconsistent with those attributed to the MPTP.

    View details for DOI 10.7554/eLife.23781

    View details for PubMedID 28186490

    View details for PubMedCentralID PMC5323039