About

Imran Rizvi is an Assistant Professor at the University of North Carolina at Chapel Hill, affiliated with the Curriculum in Toxicology & Environmental Medicine. His research focuses on identifying and photochemically targeting sources of treatment failure in cancer. His work involves the iterative and collaborative development of physiologically-relevant in vitro and in vivo tumor models, integrating principles from engineering and cancer biology to elucidate sources of treatment resistance. Rizvi's research emphasizes the identification of molecular survival pathways modulated by external cues such as flow-induced shear stress and environmental contaminants, which influence chemoresistance in ovarian cancer. Additionally, he develops optically-triggered and imaging-informed targeted combination therapies aimed at maximizing potency while minimizing off-target toxicity. These therapies leverage the mechanistically-distinct cytotoxicity of photodynamic therapy (PDT), which can reverse chemoresistance, synergize with chemotherapeutics and biologics, and overcome compensatory survival pathways.

Research topics

• Medicine
• Biology
• Internal medicine
• Pathology
• Physiology
• Cancer research
• Oncology
• Environmental health
• Bioinformatics
• Endocrinology

Selected publications

• Chronic PFAS exposure induces chemotherapy resistance by promoting mitochondria-related alterations in ovarian cancer cells

  Environmental Research · 2025-06-21 · 6 citations

  articleOpen accessSenior authorCorresponding

  Resistance to chemotherapy is a major barrier to the effective treatment of ovarian cancer; however, the role of environmental exposures in the onset of chemoresistance remains elusive. Our previous work in ovarian cancer cells suggests that short-term perfluoroalkyl substances (PFAS) exposure induce chemoresistance, potentially by influencing mitochondrial parameters, but little is known about the effects of longer-term exposures, which are more human-relevant. Since mitochondria play a critical role in determining ovarian cancer chemotherapy response, it is also important to understand the role of environmental exposures in modulating mitochondrial function. This study explored how varying durations of PFAS exposure (2-35 days) affect mitochondrial parameters known to drive chemoresistance in human ovarian cancer cell lines. An ovarian cancer cell line (OVCAR-3) that was chronically exposed to PFAS (26-35 days) was generated. Compared to short-term PFAS exposure, chronic PFAS exposures significantly increased resistance to both carboplatin and doxorubicin. Chemotherapy resistance was accompanied by increased mitochondrial superoxide production, alterations in bioenergetics, and elevated mitochondrial content. These findings suggest that PFAS exposure induces chemotherapy resistance in ovarian cancer cells in a duration-dependent manner, worsened by human-relevant chronic exposures, and that mechanisms driving these effects are influenced by the modulation of mitochondrial parameters. Future studies should focus on targeting mechanisms underlying PFAS-induced chemotherapy resistance to improve survival outcomes. Mitochondrial and chemotherapy response alterations in PFAS-exposed ovarian cancer cells after various durations of exposure compared to known mitochondrial alterations in platinum-resistant ovarian cancer. Contains Servier Medical Art stock images provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license. • An ovarian cancer cell line that was chronically exposed to perfluoroheptanoic acid (PFHpA, 26-35 days) was developed (OVCAR-3). • PFAS induce chemoresistance in ovarian cancer in a duration-dependent manner, with chronic exposure leading to the most severe effects. • Chemoresistance observed after varying durations of PFAS exposure is accompanied by mitochondria-related alterations, including ROS production, bioenergetics, and the number of mitochondria.

  PublisherDOI

• Photodynamic priming overcomes platinum resistance from short‐term exposure to select perfluoroalkyl substances in endometrial cancer cell lines

  Photochemistry and Photobiology · 2025-03-10 · 2 citations

  articleOpen accessSenior authorCorresponding

  First-line treatment for advanced-stage or recurrent endometrial cancer consists of platinum- and taxane-based chemotherapy, to which many patients will develop resistance. Determining the factors that contribute to platinum resistance and developing alternate treatment options for patients with advanced-stage gynecologic malignancies is critical to improving survival outcomes. Recently, we published the first study evaluating the contribution of perfluoroalkyl substances (PFAS) exposure to platinum resistance in endometrial cancer cell lines and found that select PFAS induce carboplatin resistance, potentially by dysregulating mitochondrial function. The present study expands upon those findings by examining the efficacy of photodynamic priming (PDP) in combination with carboplatin to overcome PFAS-induced platinum resistance. Due to the suspected role of mitochondrial dysfunction in platinum resistance, two clinically approved photosensitizers that, in part, localize to mitochondrial membranes or are synthesized in mitochondria were evaluated: benzoporphyrin derivative (BPD) and aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX), respectively. Combination of ALA-PpIX-mediated PDP + carboplatin resulted in a greater reduction in survival fraction than the same combination with BPD. While PDP with both photosensitizers reduced mitochondrial membrane potential, the reduction was greater with BPD-PDP than ALA-PpIX-PDP. These findings demonstrate that BPD-PDP and ALA-PpIX-PDP in combination with carboplatin can be used to overcome PFAS-induced platinum resistance in endometrial cancer cells.

  PublisherOA PDFDOI

• Photodynamic priming ( <scp>PDP</scp> ) targets platinum resistance from chronic perfluoroalkyl substances ( <scp>PFAS</scp> ) exposure in ovarian cancer cells

  Photochemistry and Photobiology · 2025-11-06

  articleOpen accessSenior author

  Photodynamic therapy (PDT) is a photochemistry-based treatment modality that synergizes with traditional agents and can overcome chemoresistance. Eighty percent of ovarian cancer patients develop chemoresistant disease, highlighting the need to identify sources of treatment failure and develop rational combinations. Studies have shown that perfluoroalkyl substances (PFAS) induce chemoresistance in a duration-dependent manner in OVCAR-3 cells. PFAS are widespread drinking water contaminants present in the blood of nearly all Americans. The present study evaluated the ability of photodynamic priming (PDP), a sub-cytotoxic variant of PDT, in combination with chemotherapy to overcome chemoresistance in two OVCAR-3 cell cohorts: PFAS chronically-exposed and outgrown (allowed to "recover" from chronic PFAS exposure). Effectiveness of benzoporphyrin derivative- (BPD-) or aminolevulinic acid-induced protoporphyrin IX-PDP (ALA-PpIX-PDP) was assessed in combination with carboplatin and doxorubicin. In PFAS chronically-exposed cells, BPD-PDP + carboplatin reduced survival fraction compared to carboplatin alone. Mitochondrial membrane potential also decreased significantly in both cohorts following ALA-PpIX-PDP-based combinations. PDP + doxorubicin also successfully overcame chemoresistance arising from chronic PFAS exposure but was less effective than PDP + carboplatin. Together, these findings demonstrate the efficacy of PDP-based combinations in overcoming chronic PFAS exposure-induced chemoresistance and should be explored in pre-clinical models of ovarian cancer.

  PublisherOA PDFDOI

• Photodynamic therapy simultaneously induces ferroptosis- and apoptosis-like lipid signatures in ovarian cancer cells

  Cell Death and Disease · 2025-12-10

  articleOpen accessSenior author

  Resistance to apoptosis-inducing chemotherapy is a major factor contributing to treatment failure and poor survival outcomes in high-grade serous ovarian cancer (HGSOC). Ferroptosis, a regulated form of cell death driven by lipid peroxidation, has emerged as a promising effector mechanism because it remains available in HGSOC cells with impaired apoptosis signaling. While most research has focused on pharmacological ferroptosis inducers, there is growing interest in strategies that could trigger lipid autoxidation through externally delivered energy, such as photons. Photodynamic therapy (PDT), which utilizes light and light-activatable photosensitizers to generate reactive molecular species, offers a means of initiating lipid peroxidation with a high degree of precision and minimal systemic toxicities. However, the precise lipid targets of PDT, the influence of varying tumor lipidomic landscapes, and the role of ferroptosis sensitivity on PDT-lipid interactions have yet to be elucidated. In this study, we systematically compare PDT to ferroptosis induced by the inhibition of glutathione peroxidase 4, focusing on lipid redox states and composition in HGSOC cell lines. While PDT was similarly effective in both ferroptosis-sensitive and -resistant cells, its effects on cellular lipidomes differed markedly. PDT robustly induced lipid radical formation in both cell types; however, a dose-dependent accumulation of lipid hydroxides and hydroperoxides was only observed in ferroptosis-sensitive cells rich in unsaturated phospholipids. Further analysis revealed a significant overlap in lipid oxidation targets between PDT and ferroptosis. Notably, in both cell types, and in vivo, PDT upregulated ceramides, a lipid class strongly associated with mitochondrial apoptosis. In summary, PDT exhibited comparable efficacy in both ferroptosis-sensitive and -resistant cells by triggering a combination of lipid peroxidation and ceramide upregulation, suggesting the activation of both ferroptosis and apoptosis pathways. Further studies are needed to explore the role of PDT-induced lipidomic changes in the initiation of various cell death pathways and in overcoming chemoresistance in HGSOC.

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• Mitochondrial membrane hyperpolarization modulates nuclear DNA methylation and gene expression through phospholipid remodeling

  Nature Communications · 2025-04-29 · 15 citations

  articleOpen access

  Maintenance of the mitochondrial inner membrane potential (ΔΨm) is critical for many aspects of mitochondrial function. While ΔΨm loss and its consequences are well studied, little is known about the effects of mitochondrial hyperpolarization. In this study, we used cells deleted of ATP5IF1 (IF1), a natural inhibitor of the hydrolytic activity of the ATP synthase, as a genetic model of increased resting ΔΨm. We found that the nuclear DNA hypermethylates when the ΔΨm is chronically high, regulating the transcription of mitochondrial, carbohydrate and lipid genes. These effects can be reversed by decreasing the ΔΨm and recapitulated in wild-type (WT) cells exposed to environmental chemicals that cause hyperpolarization. Surprisingly, phospholipid changes, but not redox or metabolic alterations, linked the ΔΨm to the epigenome. Sorted hyperpolarized WT and ovarian cancer cells naturally depleted of IF1 also showed phospholipid remodeling, indicating this as an adaptation to mitochondrial hyperpolarization. These data provide a new framework for how mitochondria can impact epigenetics and cellular biology to influence health outcomes, including through chemical exposures and in disease states.

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• Acute Hemichorea–Hemiballismus in Patients with Tuberculous Meningitis: An Atypical Manifestation of Stroke

  Neurology India · 2025-01-01

  articleOpen access

  We report two cases of tuberculosis meningitis patients developing hemichorea-hemiballismus during antituberculosis treatment. First, a 56-year-old woman experienced right-sided hemichorea-hemiballismus 3 months into treatment. MRI scans revealed a left thalamus and subthalamic infarct. After 10 days of continued treatment and corticosteroids, her movements subsided. Second, a 17-year-old female developed hemichorea-hemiballismus while on antituberculosis drugs and corticosteroids. MRI scans displayed ischemic lesions, optochiasmatic arachnoiditis, gyral enhancement, and a small tuberculoma. After shunt surgery and tetrabenazine treatment, she significantly improved and resumed daily activities. In conclusion, hemichorea-hemiballismus may paradoxically occur in tuberculosis meningitis patients, potentially linked to ischemic lesions in the thalamus and subthalamus.

  PublisherDOI

• Fractionated photoimmunotherapy stimulates an anti-tumour immune response: an integrated mathematical and in vitro study

  British Journal of Cancer · 2024-09-11 · 2 citations

  articleOpen access

  BACKGROUND: Advanced epithelial ovarian cancer (EOC) has high recurrence rates due to disseminated initial disease presentation. Cytotoxic phototherapies, such as photodynamic therapy (PDT) and photoimmunotherapy (PIT, cell-targeted PDT), have the potential to treat disseminated malignancies due to safe intraperitoneal delivery. METHODS: We use in vitro measurements of EOC tumour cell and T cell responses to chemotherapy, PDT, and epidermal growth factor receptor targeted PIT as inputs to a mathematical model of non-linear tumour and immune effector cell interaction. The model outputs were used to calculate how photoimmunotherapy could be utilised for tumour control. RESULTS: ) lead to limited tumour cell killing they also increased proliferation of anti-tumour immune effector cells. Model simulations demonstrated that breaking up a larger light dose into multiple lower dose fractions (vis-à-vis fractionated radiotherapy) could be utilised to effect tumour control via stimulation of an anti-tumour immune response. CONCLUSIONS: There is promise for applying fractionated PIT in the setting of EOC. However, recommending specific fractionated PIT dosimetry and timing will require appropriate model calibration on tumour-immune interaction data in human patients and subsequent validation of model predictions in prospective clinical trials.

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• <scp>PpIX</scp>‐enabled fluorescence‐based detection and photodynamic priming of platinum‐resistant ovarian cancer cells under fluid shear stress

  Photochemistry and Photobiology · 2024-08-27 · 8 citations

  articleOpen accessSenior authorCorresponding

  Over 75% percent of ovarian cancer patients are diagnosed with advanced-stage disease characterized by unresectable intraperitoneal dissemination and the presence of ascites, or excessive fluid build-up within the abdomen. Conventional treatments include cytoreductive surgery followed by multi-line platinum and taxane chemotherapy regimens. Despite an initial response to treatment, over 75% of patients with advanced-stage ovarian cancer will relapse and succumb to platinum-resistant disease. Recent evidence suggests that fluid shear stress (FSS), which results from the movement of fluid such as ascites, induces epithelial-to-mesenchymal transition and confers resistance to carboplatin in ovarian cancer cells. This study demonstrates, for the first time, that FSS-induced platinum resistance correlates with increased cellular protoporphyrin IX (PpIX), the penultimate downstream product of heme biosynthesis, the production of which can be enhanced using the clinically approved pro-drug aminolevulinic acid (ALA). These data suggest that, with further investigation, PpIX could serve as a fluorescence-based biomarker of FSS-induced platinum resistance. Additionally, this study investigates the efficacy of PpIX-enabled photodynamic therapy (PDT) and the secretion of extracellular vesicles under static and FSS conditions in Caov-3 and NIH:OVCAR-3 cells, two representative cell lines for high-grade serous ovarian carcinoma (HGSOC), the most lethal form of the disease. FSS induces resistance to ALA-PpIX-mediated PDT, along with a significant increase in the number of EVs. Finally, the ability of PpIX-mediated photodynamic priming (PDP) to enhance carboplatin efficacy under FSS conditions is quantified. These preliminary findings in monolayer cultures necessitate additional studies to determine the feasibility of PpIX as a fluorescence-based indicator, and mediator of PDP, to target chemoresistance in the context of FSS.

  PublisherOA PDFDOI

• Overcoming the effects of fluid shear stress in ovarian cancer cell lines: Doxorubicin alone or photodynamic priming to target platinum resistance

  Photochemistry and Photobiology · 2024-06-07 · 5 citations

  articleOpen accessSenior authorCorresponding

  Resistance to platinum-based chemotherapies remains a significant challenge in advanced-stage high-grade serous ovarian carcinoma, and patients with malignant ascites face the poorest outcomes. It is, therefore, important to understand the effects of ascites, including the associated fluid shear stress (FSS), on phenotypic changes and therapy response, specifically FSS-induced chemotherapy resistance and the underlying mechanisms in ovarian cancer. This study investigated the effects of FSS on response to cisplatin, a platinum-based chemotherapy, and doxorubicin, an anthracycline, both of which are commonly used to manage advanced-stage ovarian cancer. Consistent with prior research, OVCAR-3 and Caov-3 cells cultivated under FSS demonstrated significant resistance to cisplatin. Examination of the role of mitochondria revealed an increase in mitochondrial DNA copy number and intracellular ATP content in cultures grown under FSS, suggesting that changes in mitochondria number and metabolic activity may contribute to platinum resistance. Interestingly, no resistance to doxorubicin was observed under FSS, the first such observation of a lack of resistance under these conditions. Finally, this study demonstrated the potential of photodynamic priming using benzoporphyrin derivative, a clinically approved photosensitizer that localizes in part to mitochondria and endoplasmic reticula, to enhance the efficacy of cisplatin, but not doxorubicin, thereby overcoming FSS-induced platinum resistance.

  PublisherOA PDFDOI

• Abstract B111: Mechanism-informed photochemical strategies to overcome fluid shear stress-induced platinum resistance in ovarian cancer

  Cancer Research · 2024-03-04

  articleSenior author

  Abstract Background: Over 75% of patients with disseminated ovarian cancer develop resistance to platinum-based chemotherapies (carboplatin or cisplatin). Patients with a high volume of malignant ascites or excessive fluid buildup in the peritoneum are more likely to present with primary platinum-resistant disease. It is hypothesized that the physical forces generated by ascites may contribute to the dissemination and progression of ovarian cancer. Our research group has shown that fluid shear stress (FSS) induces carboplatin resistance and a motile and aggressive phenotype in monolayer cultures and 3D models for adherent ovarian cancer. In this study, the effects of FSS on treatment response to cisplatin and doxorubicin were examined. The latter is used to manage recurrent platinum-resistant disease. Changes in mitochondrial function under FSS as they relate to platinum resistance were also characterized. Finally, the use of photodynamic therapy (PDT), which utilizes 690 nm light and a clinical photosensitizer benzoporphyrin derivative (BPD) to locally generate cytotoxic reactive molecular species as a means of overcoming FSS-induced platinum resistance, was explored. Methods: Human epithelial ovarian adenocarcinoma cells OVCAR-3 and Caov-3 (ATCC) were cultured in tissue culture plates (static culture) or chamber slides (ibidi) connected to a perfusion pump for 48 h (flow rate: 0.11 mL/min, shear stress: 0.41 dyn/cm2). Cells in static and flow cultures were exposed to cisplatin, doxorubicin, BPD-PDT or combinations thereof and survival fractions were measured 72 h post-treatment. Mitochondrial membrane potential was measured using JC-1 fluorescence assay, and mitochondrial DNA (mtDNA) copy number was quantified using qPCR. ATP content per cell was measured with a CellTiterGlo luminescence assay. Results: OVCAR-3 and Caov-3 cells grown under FSS developed significant resistance to cisplatin. Specifically, 3.13 µM cisplatin induced a 50% decrease in the survival fraction in OVCAR-3 static cultures but failed to decrease the survival fraction under flow. In contrast to these findings with platins, no resistance to doxorubicin was observed under flow. Evaluation of the mitochondrial function revealed increased ATP content and mtDNA copy number in flow cultures, suggesting that increased mitochondrial activity may contribute to platinum resistance. Finally, low-dose BPD-PDT (IC10, 0.15 J/cm2) enhanced the efficacy of cisplatin in OVCAR-3 cells under flow, indicating that PDT is a viable strategy to sensitize tumors exposed to FSS to platinum-based chemotherapy. Conclusions: Our data suggest that ovarian cancer cells that acquired resistance to platinum due to FSS remain sensitive to doxorubicin. Changes in mitochondrial function, including increased ATP content per cell and mtDNA copy number, have been identified as potential contributing factors to platinum resistance under FSS. Finally, low-dose BPD-PDT can be used to re-sensitize cells to cisplatin and overcome platinum resistance. Citation Format: Marta Overchuk, Brittany P. Rickard, Justin Tulino, Frances S. Ligler, Imran Rizvi. Mechanism-informed photochemical strategies to overcome fluid shear stress-induced platinum resistance in ovarian cancer [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr B111.

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Recent grants

• Targeting Fluid Stress-induced Chemoresistance in a 3D Carcinomatosis Perfusion Model Using Mechanism-based Photo-immunoconjugate Nanoparticles

  NIH · $2.2M · 2023–2027

• NIH Grant K99CA175292

  NIH · $350k · 2016

• Targeting Determinants of OvCa Metastases in Engineered 3D Microfluidic Platforms

  NIH · $746k · 2016–2020

Frequent coauthors

• Tayyaba Hasan

  Massachusetts General Hospital

  393 shared

• Jonathan P. Celli

  University of Massachusetts Boston

  175 shared

• Mustafa Kemal Ruhi

  North Carolina State University

  107 shared

• Huang‐Chiao Huang

  University of Maryland, College Park

  105 shared

• Sriram Anbil

  University of Pennsylvania

  98 shared

• William J. Polacheck

  North Carolina State University

  74 shared

• Brittany P. Rickard

  University of North Carolina at Chapel Hill

  72 shared

• Conor L. Evans

  Harvard University

  59 shared

Education

• Ph.D., Toxicology

  University of North Carolina at Chapel Hill

  2005

• M.S., Toxicology

  University of North Carolina at Chapel Hill

  2001

• B.S., Toxicology

  University of North Carolina at Chapel Hill

  1999