About

Parish Sedghizadeh, DDS, MS, is a Professor of Clinical Dentistry at the University of Southern California (USC), Ostrow School of Dentistry. He serves as the Director of the USC Center for Biofilms and Co-Chair of the Department of Diagnostic Sciences, Anesthesia and Emergency Medicine. Dr. Sedghizadeh received his Bachelor of Science degree in biology from UCLA and his Doctor of Dental Surgery from USC. He pursued specialty training in Oral and Maxillofacial Pathology at Ohio State University, where he also earned a Master of Science degree in Oral Biology, completed a fellowship in the American Academy of Oral and Maxillofacial Pathology, and attained board certification. His research, clinical practice, and projects focus on the characterization and treatment of maxillofacial pathology and microbial biofilm infections, with particular emphasis on jaw osteomyelitis and osteonecrosis, where he has developed novel bone-targeted antimicrobial therapeutics. Dr. Sedghizadeh conducts research, publishes, consults, and teaches in the fields of oral and maxillofacial pathology, radiology, and medicine, maintaining an active clinical practice.

Research topics

• Pathology
• Medicine
• Radiology
• Dentistry
• Surgery
• Anatomy
• Dermatology

Selected publications

• Abstract 7524: Genetically defined organoid systems uncover PIK3CA-mediated suppression of an oral-immune program during early squamous neoplastic evolution

  Cancer Research · 2026-04-03

  article

  Abstract Head and neck squamous cell carcinoma (HNSCC) is an aggressive and lethal neoplasm, yet its early neoplastic transformation mechanisms remain poorly defined. Despite extensive genomic characterization, translation of these molecular insights into clinical practice has been limited. A critical barrier has been the absence of physiologically relevant human models capable of faithfully recapitulating the stepwise progression from precursor lesions to invasive tumors while enabling rigorous interrogation of genotype-phenotype relationships. Here, we developed two complementary, cross-species, genetically defined organoid systems—a genome-sequenced patient-derived platform spanning normal tissue, precursor lesions, and tumors, and a CRISPR/Cas9-engineered human and mouse organoid platform targeting key HNSCC drivers (TP53, CDKN2A, PIK3CA) to reconstruct the continuum of squamous malignant transformation. Using these models, we uncovered critical insights into early neoplastic evolution. TP53/CDKN2A double-knockout (DKO) organoids exhibited morphological dysplasia, hyperproliferation, loss of squamous differentiation, and tumorigenicity—phenotypes further exacerbated by introducing mutant PIK3CAE545K (DKOP). Single-cell RNA sequencing of DKO and DKOP organoids revealed expansion of quiescent basal and proliferative squamous populations and depletion of differentiated cells. Notably, an Oral-Immune transcriptional program characteristic of normal squamous epithelium was attenuated in DKO organoids and further diminished in DKOP. The Oral-Immune program was strongly correlated with intratumoral T-cell infiltration in HNSCC, marked by enrichment of cytotoxic and proliferative CD8+ subsets and upregulation of IFN-pathway and cytotoxic effector genes. Strikingly, across 46 ICB-treated cohorts, its strongest association with therapeutic response occurred in an HNSCC cohort, where it outperformed 17 established immune gene-expression signatures, including IFNG and PD-L1. Both CD8+ T-cell scores and the Oral-Immune score were inversely correlated with PIK3CA mutation status. Mutant PIK3CAE545K suppressed Oral-Immune program genes in HNSCC, and this effect was reversible with PI3K inhibition. Functionally, PIK3CA mutations reduced CD8+ T-cell infiltration in both in vitro CD8+ T cell-organoid coculture assays and in vivo orthotopic allograft models. Together, these findings identify the Oral-Immune program as a key determinant of immune-inflamed tumor states, reveal PIK3CA mutations as drivers of immune evasion and diminished immunotherapy responsiveness through suppression of this program, and underscore the power of genetically defined organoid models for dissecting early cancer evolution. Citation Format: Hua Zhao, Young Min Park, Yueyuan Zheng, Qiong Mao, Hao Wu, Fanyi Mo, Uttam K. Sinha, Parish Sedghizadeh, De-Chen Lin. Genetically defined organoid systems uncover PIK3CA-mediated suppression of an oral-immune program during early squamous neoplastic evolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7524.

  PublisherDOI

• Genetically Defined Organoid Models Reveal Mechanisms Driving Squamous Cell Neoplastic Evolution and Identify Potential Therapeutic Vulnerabilities

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-01-22 · 1 citations

  preprintOpen access

  ABSTRACT Upper aerodigestive squamous cell carcinoma (UASCC) is an aggressive and lethal neoplasm, with its early neoplastic transformation mechanisms remaining poorly understood. Here, we characterize over 25 genetically-defined organoid models derived from murine and human oral/esophageal tissues harboring key driver mutations. Double knockout of TP53 and CDKN2A induced morphological dysplasia, hyperproliferation, loss of squamous differentiation, and tumorigenicity, which were further exacerbated by additional driver mutations (e.g., PIK3CA , NOTCH1 , KMT2C ). Single-cell analysis revealed an expansion of quiescent basal cells and proliferative squamous cells, alongside a loss of differentiated squamous cells during malignant transformation. A distinct senescence program, regulated by ANXA1, was markedly diminished during early neoplastic evolution. Mechanistically, the ANXA1-SMAD3-p27 KIP1 pathway was identified as a critical regulator of this senescence program, acting to suppress neoplastic features in organoid models. Lastly, our high-throughput, single-organoid-resolution drug screens unexpectedly revealed PIK3CA -driven organoids exhibited sensitivity to Mitomycin C and Onalespib. This study provides novel mechanistic insights into early neoplastic evolution and underscores the value of genetically-defined organoid models for investigating cancer biology and identifying targeted therapies.

  PublisherDOI

• Mandibular Osteomas: Report of Two Cases With Surgical Management

  Clinical Case Reports · 2025-11-01

  articleOpen access

  Solitary peripheral osteomas of the mandible can cause facial deformity and are best evaluated using CT scans, which reveal well-circumscribed, hyperdense masses. Importantly, osteomas warrant prompt systematic evaluation to rule out Gardner's syndrome, especially when numerous lesions are present. Surgical excision is an effective treatment with no recurrence observed in these cases, highlighting the importance of early diagnosis and intervention for optimal functional and esthetic outcomes.

  PublisherOA PDFDOI

• An Unusual Case of Periapical Cemento‐Osseous Dysplasia

  Clinical Case Reports · 2025-10-01

  articleOpen accessSenior author

  Periapical cemento-osseous dysplasia (PCOD) is a benign fibro-osseous condition often discovered incidentally during radiographic examinations. Accurate diagnosis is crucial to prevent unnecessary treatment. Conservative management with regular monitoring is typically sufficient, as illustrated in this case involving a 62-year-old female patient with a two-decade follow-up.

  PublisherOA PDFDOI

• Evaluating the Accuracy of an Artificial Intelligence-Based Application for Diagnosing Temporomandibular Disorders

  Journal of the California Dental Association · 2025-07-31 · 1 citations

  articleOpen accessSenior author

  Background Temporomandibular disorders (TMD) present a diagnostic challenge, particularly for non-specialists, due to the complexity and variability of symptoms. This study evaluates the diagnostic accuracy of the AI-driven myTMJ© application (myTMJ©) by comparing its outputs to clinical diagnoses made by board-certified orofacial pain specialists at the Herman Ostrow School of Dentistry of USC. The app’s ability to identify the diagnosis most closely associated with a user’s chief complaint was assessed.Methods To test whether the observed accuracy of myTMJ differs from a hypothesized benchmark of 90%, a one-proportion z-test was conducted at a significance level of α = 0.05 (two-sided). Demographic characteristics, including age and gender, were summarized for the sample (n = 110). Continuous variables were reported as medians with interquartile ranges (IQR), while categorical variables were summarized as frequencies and percentages. The study included 110 patients, 30% male, with a median age of 34.0 years (IQR: 26.0–47.0).Results Of the 110 app-generated diagnoses, 105 (95.5%) were confirmed accurate by clinical diagnosis. The observed accuracy was significantly higher than the hypothesized 90%, as evidenced by a p-value of 0.036. The 95% confidence interval for the observed accuracy was [0.923, 0.997], further supporting the app’s high diagnostic performance.Conclusion These findings underscore myTMJ’s potential as a reliable tool for diagnosing TMD and orofacial pain. Notably, users answered questions under the supervision of orofacial pain residents, which may have contributed to high accuracy.Practical Implications Future studies should incorporate a broader sample and evaluate the app’s performance in an unsupervised setting to assess real-world diagnostic accuracy.

  PublisherDOI

• Patient-derived tumor organoids to model drug response in gastric cancer

  Cell Reports Medicine · 2024-07-01 · 9 citations

  articleOpen accessCorresponding

  Gastric cancer poses diverse treatment challenges due to its high tumor heterogeneity. Through the use of patient-derived tumor organoid (PDO) models, new research1Zhao Y. Li S. Zhu L. Huang M. Xie Y. Song X. Chen Z. Lau H.C.-H. Sung J.J.-Y. Xu L. Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer.Cell Rep. Med. 2024; 5: 101627https://doi.org/10.1016/j.xcrm.2024.101627Abstract Full Text Full Text PDF Google Scholar has identified genes and molecular signatures that are predictive of chemotherapeutic response, providing valuable insights for clinical management and translational advancements. Gastric cancer poses diverse treatment challenges due to its high tumor heterogeneity. Through the use of patient-derived tumor organoid (PDO) models, new research1Zhao Y. Li S. Zhu L. Huang M. Xie Y. Song X. Chen Z. Lau H.C.-H. Sung J.J.-Y. Xu L. Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer.Cell Rep. Med. 2024; 5: 101627https://doi.org/10.1016/j.xcrm.2024.101627Abstract Full Text Full Text PDF Google Scholar has identified genes and molecular signatures that are predictive of chemotherapeutic response, providing valuable insights for clinical management and translational advancements. Gastric cancer (GC) presents a significant global health challenge, with over a million new cases diagnosed annually and approximately 800,000 deaths each year.2Bray F. Laversanne M. Sung H. Ferlay J. Siegel R.L. Soerjomataram I. Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.CA. Cancer J. Clin. 2024; 74: 229-263https://doi.org/10.3322/caac.21834Crossref PubMed Scopus (192) Google Scholar The majority of GC patients are diagnosed with locally advanced disease, for which surgical resection combined with perioperative chemotherapy (e.g., 5-fluorouracil [5-FU], cisplatin, and oxaliplatin) remains the primary curative option.3Cunningham D. Allum W.H. Stenning S.P. Thompson J.N. Van de Velde C.J.H. Nicolson M. Scarffe J.H. Lofts F.J. Falk S.J. Iveson T.J. et al.Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer.N. Engl. J. Med. 2006; 355: 11-20https://doi.org/10.1056/NEJMoa055531Crossref PubMed Scopus (5292) Google Scholar Despite the establishment of histological classification4Laurén P. The Two Histological Main Types of Gastric Carcinoma: Diffuse and So-Called Intestinal-Type Carcinoma. An Attempt at a Histo-Clinical Classification.Acta Pathol. Microbiol. Scand. 1965; 64: 31-49https://doi.org/10.1111/apm.1965.64.1.31Crossref PubMed Scopus (5379) Google Scholar and molecular subtypes,5The Cancer Genome Atlas Research NetworkComprehensive molecular characterization of gastric adenocarcinoma.Nature. 2014; 513: 202-209https://doi.org/10.1038/nature13480Crossref PubMed Scopus (4718) Google Scholar the high variability in chemotherapy responses among GC patients remains poorly understood. Patient-derived tumor organoids (PDOs) preserve key genomic and epigenomic abnormalities of the parental tumors, maintaining histopathological characteristics of the modeled specimens.6Lo Y.-H. Karlsson K. Kuo C.J. Applications of Organoids for Cancer Biology and Precision Medicine.Nat. Cancer. 2020; 1: 761-773https://doi.org/10.1038/s43018-020-0102-yCrossref PubMed Scopus (83) Google Scholar These features make organoid modeling a valid tool for investigating treatment response in patient tumors.6Lo Y.-H. Karlsson K. Kuo C.J. Applications of Organoids for Cancer Biology and Precision Medicine.Nat. Cancer. 2020; 1: 761-773https://doi.org/10.1038/s43018-020-0102-yCrossref PubMed Scopus (83) Google Scholar Indeed, several studies have utilized organoid modeling to interrogate drug responsiveness among GC patients,7Yan H.H.N. Siu H.C. Law S. Ho S.L. Yue S.S.K. Tsui W.Y. Chan D. Chan A.S. Ma S. Lam K.O. et al.A Comprehensive Human Gastric Cancer Organoid Biobank Captures Tumor Subtype Heterogeneity and Enables Therapeutic Screening.Cell Stem Cell. 2018; 23: 882-897.e11https://doi.org/10.1016/j.stem.2018.09.016Abstract Full Text Full Text PDF PubMed Scopus (450) Google Scholar,8Seidlitz T. Merker S.R. Rothe A. Zakrzewski F. von Neubeck C. Grützmann K. Sommer U. Schweitzer C. Schölch S. Uhlemann H. et al.Human gastric cancer modelling using organoids.Gut. 2019; 68: 207-217https://doi.org/10.1136/gutjnl-2017-314549Crossref PubMed Scopus (219) Google Scholar,9Steele N.G. Chakrabarti J. Wang J. Biesiada J. Holokai L. Chang J. Nowacki L.M. Hawkins J. Mahe M. Sundaram N. et al.An Organoid-Based Preclinical Model of Human Gastric Cancer.Cell. Mol. Gastroenterol. Hepatol. 2019; 7: 161-184https://doi.org/10.1016/j.jcmgh.2018.09.008Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar significantly advancing our understanding of GC biology and therapeutic resistance. Nevertheless, key questions remain to be addressed. (1) What are the genomic/transcriptomic determinants of drug sensitivity of GC? (2) Can gene signatures serve as predictive biomarkers for treatment response in GC patients? (3) Is ex vivo PDO drug response data reproducible in vivo, a key property for its translational application? New research published in Cell Reports Medicine1Zhao Y. Li S. Zhu L. Huang M. Xie Y. Song X. Chen Z. Lau H.C.-H. Sung J.J.-Y. Xu L. Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer.Cell Rep. Med. 2024; 5: 101627https://doi.org/10.1016/j.xcrm.2024.101627Abstract Full Text Full Text PDF Google Scholar has specifically taken on these questions by performing histopathological, genomic, transcriptomic, and therapeutic analyses of a significant number of GC PDOs. The authors established 57 organoids from 73 GC patient specimens, covering multiple stomach sites and different TNM stages. A detailed histopathologic analysis confirmed that PDOs recapitulated the histologies of their original tumors in a subtype-specific manner. For example, PDOs derived from intestinal-type GC were characterized by single-layered or cribriform glandular morphologies, featuring cells arranged to form multiple luminal structures of variable dimensions. In comparison, those derived from diffuse-type GC presented with loosely-cohesive to solid cell clusters or cystic configurations. Despite some inconsistencies, these data underscore that organoid cultures maintain the histopathologic features of their parental GC tumors. The team then investigated the responsiveness of GC PDOs to 6 common chemotherapeutics for GC patients. The authors rigorously assayed drug sensitivity by independent measurements (AUC values and IC50 values) across 2 different passages of each organoid line and along 2 sets of drug concentrations. After ensuring the robustness of the assay, they analyzed RNA sequencing data to correlate gene expression changes with drug responsiveness variability in matched PDOs. Pathway enrichment analysis revealed upregulation of the p53 signaling pathway and cellular senescence in 5-FU-sensitive PDOs. By contrast, 5-FU-resistant PDOs showed strong enrichment of tumor-invasion- and stemness-related pathways, such as NOTCH signaling and WNT signaling. Similarly, signaling pathways enriched for PDOs with differential responses to oxaliplatin were also identified. From significantly enriched pathway genes, several were selected for functional experimentation to test for their contribution to drug responsiveness. Notably, knockout of MSMB or S1PR4 (5-FU-sensitive genes) by CRISPR-Cas9 editing significantly decreased the sensitivity of PDOs to 5-FU treatment. Conversely, knockout of FKBP10 (a 5-FU-resistant gene) conferred sensitivity to 5-FU treatment on PDOs. Likewise, genes involved in oxaliplatin response (MYO1A and NDUFA4L2) were also validated. These results are significant since they demonstrate the biological regulation of these genes on chemotherapeutic sensitivity in GC PDOs. Employing the recursive feature elimination method, the researchers explored gene-expression-based biomarkers that discriminated sensitive PDO lines from lines that were resistant to 5-FU treatment. A panel of 9 genes was identified and verified to have high discriminative AUC values. Similarly, a panel of 6 genes was established to predict responsiveness to oxaliplatin treatment. These predictive gene signatures were further validated using The Cancer Genome Atlas cohort, wherein patients treated with 5-FU or oxaliplatin were stratified into sensitive- and resistant-like groups based on gene signature scores. Notably, in the 5-FU-treated cohort, sensitive-like patients showed significantly better progression-free survival. This 5-FU gene signature also showed the highest AUC values for predicting drug sensitivity when compared against published gene signatures. To validate the drug response data obtained ex vivo, the authors established matched PDO xenograft (PDOX) in immunodeficient mice for chemotherapeutic treatment. Importantly, in each of the 5 PDO-PDOX paired models, drug responsiveness was highly consistent between in vitro and in vivo assays. The PDO drug testing results were further subjected to the last, perhaps most important, validation using real-life clinical outcome data from original GC patients. Specifically, 12 PDO-matched patients received peri- or postoperative adjuvant chemotherapy with oxaliplatin and 5-FU and were followed for up to 49 months. Strikingly, 11 out of 12 patients exhibited drug response results consistent with their corresponding PDO lines. These data highlight that PDOs are robust and valid tools for cancer drug screening and drug response prediction. Lastly, the authors explored the impact of the tumor microenvironment on drug responsiveness by co-culturing cancer-associated fibroblasts (CAFs) with autologous PDOs. Indeed, the presence of CAFs substantially increased the drug resistance of PDOs to 5-FU and oxaliplatin treatment. Interestingly, this pro-resistance effect was also seen when PDOs were co-cultured with heterologous CAF lines. These findings align with the recognized role of CAFs in enhancing drug resistance within the tumor microenvironment.10Saw P.E. Chen J. Song E. Targeting CAFs to overcome anticancer therapeutic resistance.Trends Cancer. 2022; 8: 527-555https://doi.org/10.1016/j.trecan.2022.03.001Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar In summary, upon establishing a sizable PDO biobank for GC patients, this study identified and verified genes and molecular signatures that are predictive of chemotherapeutic response. Co-culturing with CAFs highlighted the role of the tumor microenvironment in mediating drug resistance. These results confirm the robustness of PDO models for cancer drug screening and response prediction. Moving forward, single-cell multi-omic analyses of PDOs will identify mechanisms underlying drug responsiveness in an unprecedented resolution. Moreover, single-cell CRISPR screening on PDO models will causally pinpoint genes responsible for drug resistance in an unbiased manner. These exciting new molecular technologies, together with sophisticated organoid modeling of the tumor microenvironment, will greatly improve precision medicine for cancer patients. D.-C.L. was supported by the Ming Hsieh Institute Research Award and the NIH under awards R37CA237022, R01DK135562, and R01DE033648. The authors declare no competing interests. Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancerZhao et al.Cell Reports MedicineJuly 3, 2024In BriefYi et al. present the establishment of a biobank of gastric cancer organoids derived from patients. These organoids mirror the complex dynamics of chemotherapy response. It may offer a valuable tool for the refinement of personalized treatments and the prediction of individual patient responses to chemotherapy. Full-Text PDF Open Access

  PublisherDOI

• Bilateral dens evaginatus and associated cystic pathology: An unusual case report

  Clinical Case Reports · 2024-04-01 · 1 citations

  articleOpen accessSenior author

  Dens evaginatus (DE) presents a clinical conundrum due to its fragility and propensity to cause pulpal and periapical complications. Clinicians should heed the presence of DE during clinical examinations and avoid unnecessary intervention.

  PublisherOA PDFDOI

• Diagnosis and treatment of mixed salivary gland tumor previously diagnosed as cutaneous chondroid syringoma proximal to the oral commissure: A case report

  Clinical Case Reports · 2024-03-28 · 2 citations

  articleOpen accessSenior author

  Subcutaneous tumors of the head and neck resembling cutaneous mixed tumors may be misdiagnosed pleomorphic adenomas of salivary gland origin. Physicians should consider salivary mixed tumors in the differential diagnosis for suspected cutaneous tumors.

  PublisherOA PDFDOI

• Artificial Intelligence for Rapid Clinical Diagnosis in Oral Medicine

  Oral Surgery Oral Medicine Oral Pathology and Oral Radiology · 2023-02-01 · 5 citations

  articleSenior author
  PublisherDOI

• Real-Time Impedance-Based Monitoring of the Growth and Inhibition of Osteomyelitis Biofilm Pathogen Staphylococcus aureus Treated with Novel Bisphosphonate-Fluoroquinolone Antimicrobial Conjugates

  International Journal of Molecular Sciences · 2023-01-19 · 9 citations

  articleOpen access1st author

  Osteomyelitis is a limb- and life-threatening orthopedic infection predominantly caused by Staphylococcus aureus biofilms. Bone infections are extremely challenging to treat clinically. Therefore, we have been designing, synthesizing, and testing novel antibiotic conjugates to target bone infections. This class of conjugates comprises bone-binding bisphosphonates as biochemical vectors for the delivery of antibiotic agents to bone minerals (hydroxyapatite). In the present study, we utilized a real-time impedance-based assay to study the growth of Staphylococcus aureus biofilms over time and to test the antimicrobial efficacy of our novel conjugates on the inhibition of biofilm growth in the presence and absence of hydroxyapatite. We tested early and newer generation quinolone antibiotics (ciprofloxacin, moxifloxacin, sitafloxacin, and nemonoxacin) and several bisphosphonate-conjugated versions of these antibiotics (bisphosphonate-carbamate-sitafloxacin (BCS), bisphosphonate-carbamate-nemonoxacin (BCN), etidronate-carbamate-ciprofloxacin (ECC), and etidronate-carbamate-moxifloxacin (ECX)) and found that they were able to inhibit Staphylococcus aureus biofilms in a dose-dependent manner. Among the conjugates, the greatest antimicrobial efficacy was observed for BCN with an MIC of 1.48 µg/mL. The conjugates demonstrated varying antimicrobial activity depending on the specific antibiotic used for conjugation, the type of bisphosphonate moiety, the chemical conjugation scheme, and the presence or absence of hydroxyapatite. The conjugates designed and tested in this study retained the bone-binding properties of the parent bisphosphonate moiety as confirmed using high-performance liquid chromatography. They also retained the antimicrobial activity of the parent antibiotic in the presence or absence of hydroxyapatite, albeit at lower levels due to the nature of their chemical modification. These findings will aid in the optimization and testing of this novel class of drugs for future applications to pharmacotherapy in osteomyelitis.

  PublisherOA PDFDOI

Recent grants

• Bone targeted antimicrobials for biofilm-mediated osteolytic infection treatment

  NIH · $150k · 2016–2018

• Bone targeted antimicrobials for biofilm-mediated osteolytic infection treatment

  NIH · $1.5M · 2016–2021

Frequent coauthors

• Christoph Schaudinn

  Robert Koch Institute

  22 shared

• Carl M. Allen

  22 shared

• R.G.G. Russell

  20 shared

• Adam Junka

  Wroclaw Medical University

  18 shared

• John R. Kalmar

  The Ohio State University

  17 shared

• Amita Gorur

  Howard Hughes Medical Institute

  16 shared

• Charles F. Shuler

  University of British Columbia

  14 shared

• J. William Costerton

  13 shared

Education

• DDS, Dentistry

  University of Southern California

• MS, Oral and Maxillofacial Pathology

  Ohio State University

• BS, Biology

  University of California, Los Angeles