About

Scott Diehl is a faculty member at Rutgers School of Dental Medicine, serving in the Department of Oral Biology. His research primarily focuses on genetics related to inherited human diseases, with specific emphasis on orofacial clefts and neuropathic pain. He is currently the Principal Investigator of a large study on Trigeminal Neuralgia, involving Whole Genome Sequencing of 100 patients, utilizing advanced AI algorithms and bioinformatics tools to identify rare causative variants within large genomic datasets. His educational background includes a Bachelor of Science from the State University of New York at Stony Brook, a PhD from the University of Texas at Austin, and a postdoctoral fellowship at the University of Massachusetts, Amherst. He has also held research positions at the University of Michigan, Ann Arbor. His research interests extend to various areas including neuropathic pain, periodontal disease, oral and pharyngeal cancer, nasopharyngeal carcinoma, non-syndromic cleft lip and palate, and the health effects of air pollution. Dr. Diehl has contributed to understanding the genetic factors involved in these conditions and has published extensively on these topics.

Research topics

• Medicine
• Internal medicine
• Dentistry
• History
• Biology
• Ancient history
• Genetics
• Mathematics
• Dermatology
• Oncology
• Pathology
• Neuroscience
• Geometry

Selected publications

• Pharmacogenetic associations of CYP2D6 and CYP2C19 variants with anticholinergic drug burden and hyposalivation

  Frontiers in Pharmacology · 2025-11-19

  articleOpen access

  Introduction Anticholinergic medications frequently cause hyposalivation (decreased saliva flow) through parasympathetic inhibition. This adverse effect is related to anticholinergic burden, reflecting the cumulative exposure to drugs with anticholinergic properties. Genetic variation in CYP genes, which encode drug-metabolizing enzymes, alters drug metabolism, potentially influencing systemic anticholinergic burden. This study investigated whether polymorphisms in the CYP2D6 and CYP2C19 genes are associated with anticholinergic burden and hyposalivation. Methods Adults taking at least one CYP substrate anticholinergic medication reporting xerostomia (oral dryness) were recruited. Anticholinergic burden was quantified using the Anticholinergic Drug Scale (ADS) and Serum Anticholinergic Activity (SAA). Salivary assessment included unstimulated whole saliva (UWS) and minor saliva flow (MSF). Participants were genotyped for functional variants of CYP2D6 and CYP2C19 . Results CYP2D6 rs28371725 polymorphism was associated with low MSF and increased SAA in severe hyposalivation (genotype relative risk: 12.75, 95% CI 1.45–112.12). Additionally, variants (rs28371706, rs5030655) were associated with high ADS scores. Individuals with reduced CYP2D6 activity presented with higher systemic exposure and a greater anticholinergic burden for a given dose, as reflected by higher ADS and SAA. CYP2C19 polymorphisms showed no strong associations with salivary outcomes or anticholinergic burden. Conclusion Genetic variation in CYP2D6 contributes to interindividual differences in systemic anticholinergic burden and hyposalivation. Pharmacogenetic profiling of CYP450 genes may help identify patients at risk of xerostomia from anticholinergic therapy, supporting more personalized and optimized anticholinergic prescribing.

  PublisherDOI

• A Rose by Any Other Name: The Long Intricate History of Localized Aggressive Periodontitis

  2024 · 1 citations

  Senior authorCorresponding
  • History
  • Ancient history
  • Medicine

  This narrative review challenges the recent World Workshop Consensus (WWC) conferences failure to classify aggressive periodontitis (AP) in young adults as distinct from adult periodontitis. Deficiencies in the consensus process, results of these deficiencies, and their impact on disease classification are presented. Support for retaining localized aggressive periodontitis (LAgP) in adolescents as a unique disease, focuses on the; 1) age of onset, 2) rate of bone loss in those affected, and 3) unique microbiological etiological associations. Examples of, 1) unique clinical signs and symptoms of LAgP are presented, and 2) the microbial subgingival consortia that precedes these clinical signs and symptoms are described. Tables show, 1) decreased publications for AP since publication of WWC guidelines and 2) Bradford-Hill guidelines that support the unique etiological consortia replicated in clinically well-defined longitudinal studies. The review describes major deficiencies in the WWC as compared to other medically-related well-run consensus conferences that, 1) set pre-conference standards for 70 – 80% agreement of expert participants, and 2) published the dissenting point of view. In contrast, the WWC conference was decided by a mere majority, and never presented the dissenting view. The review concludes that averaging of mean pocket depth reduction, or attachment gain can misrepresent disease and/or success of treatment in aggressive diseases. In contrast, clinical assessment of time to recurrence of subgingival re-infection with possible translocation of oral microbes to distant sites is presented as an alternative measurement of success. Other questions and future directions are presented.

  PublisherOA PDFDOI

• A Rose by Any Other Name: The Long Intricate History of Localized Aggressive Periodontitis

  Pathogens · 2024-09-29 · 3 citations

  reviewOpen accessSenior author

  This review addresses the recent World Workshop Consensus Conference (WWCC) decision to eliminate Localized Aggressive Periodontitis (LAgP) in young adults as a distinct form of periodontitis. A “Consensus” implies widespread, if not unanimous, agreement among participants. However, a significant number of attendees were opposed to the elimination of the LAgP classification. The substantial evidence supporting a unique diagnosis for LAgP includes the (1) incisor/molar pattern of disease, (2) young age of onset, (3) rapid progression of attachment and bone loss, (4) familial aggregation across multiple generations, and (5) defined consortium of microbiological risk factors including Aggregatibacter actinomycetemcomitans. Distinctive clinical signs and symptoms of LAgP are presented, and the microbial subgingival consortia that precede the onset of signs and symptoms are described. Using Bradford–Hill guidelines to assess causation, well-defined longitudinal studies support the unique microbial consortia, including A. actinomycetemcomitans as causative for LAgP. To determine the effects of the WWCC elimination of LAgP on research, we searched three publication databases and discovered a clear decrease in the number of new publications addressing LAgP since the new WWCC classification. The negative effects of the WWCC guidelines on both diagnosis and treatment success are presented. For example, due to the localized nature of LAgP, the practice of averaging mean pocket depth reduction or attachment gain across all teeth masks major changes in disease recovery at high-risk tooth sites. Reinstating LAgP as a distinct disease entity is proposed, and an alternative or additional way of measuring treatment success is recommended based on an assessment of the extension of the time to relapse of subgingival re-infection. The consequences of the translocation of oral microbes to distant anatomical sites due to ignoring relapse frequency are also discussed. Additional questions and future directions are also presented.

  PublisherOA PDFDOI

• Role of common and rare genetic variants in the aetiology of trigeminal neuralgia

  medRxiv · 2024-07-16

  preprintOpen accessSenior authorCorresponding

  Summary Background Trigeminal neuralgia (TN) is characterized by repeated paroxysmal attacks of severe facial pain usually lasting 1-3 minutes. Lifetime prevalence is ca.3 per 1,000, more common in women, and with onset generally in middle age. Medications usually provide relief in the early stages of the disorder, but for many patients, severe drug side effects emerge and medically intractable pain returns, sometimes lasting for life. Some patients present with paroxysmal pain predominantly while others also experience substantial concomitant constant facial pain. Some patients have a history of a blood vessel compressing and damaging their trigeminal nerve (neurovascular compression, NVC). For these “classical” cases, surgery often provides complete or substantial pain relief for many years. “Idiopathic” cases without NVC or any other apparent cause also occur. NVC was previously observed to be less frequent in females who had early age of onset and these patients may constitute a unique subgroup. Our aim was to evaluate the role of inherited genetic variation in the aetiology of TN in patient subgroups based on age of onset, presence of NVC and sex. Methods To maximize aetiological homogeneity, only patients with predominantly paroxysmal pain and minimal concomitant continuous pain were included in the analysis. Conditions known to cause secondary TN such as tumors or multiple sclerosis were excluded. The GWAS analysis was based on 626 TN patients and 827 Control subjects of European ancestry recruited in Canada, the UK, and US. A Genome-Wide Association Study (GWAS) analysis was performed using Affymetrix’s Precision Medicine arrays yielding 7,781,254 biallelic DNA variants available after Quality Control (QC) and imputation. Rare damaging mutations in genes with functions relevant to the biology of TN were identified in Whole Genome Sequencing (WGS) genomic DNA of 100 patients using a novel strategy based on overlap of symptoms of TN with symptoms of known genetic disorders. Findings The GWAS analysis revealed associations at eight genome locations including near LRP1B (P-value 6.3 X 10 -15 ), a gene important for repair of myelin sheath injury that has been previously proposed as a target for the treatment of neuropathic pain. Associations were also found for the potassium channel gene KCNK10 , and for CHL1, CUX1, SGMS1 and ZNF804B genes, all genes with neural functions potentially relevant to the aetiology of TN. In addition, high-risk genotypes at the CUX1 and KCNK10 genes exhibit significant interactions with patients’ sex and the presence or absence of NVC (P-values 0.005 and 0.017, respectively). Whole genome sequencing of 100 TN patients revealed mutations in ion channel genes TRPM4 (six patients), SCN10A and SCNN1B (five patients), CACNA1F, CACNA1S and SCN5A (four patients) and CACNA1H , SCN2A and SCN9A (three patients). Female patients with onset prior to age 46 had more mutated genes with myelin-related functions (P-value 0.004) and associated with epilepsy or seizure (P-value 0.03) than older onset females and males of any onset age. Interpretation Risk of TN in patients presenting with paroxysmal pain only is associated with both common genetic variants and with rare mutations. Some high-risk genotypes have significant interactions with sex and NVC. Evidence of the condition’s heterogeneous genetic aetiology should be considered when evaluating novel therapies. Funding Grants from the William H. and Leila A. Cilker Genetics Research Program of the Facial Pain Research Foundation, The Foundation of the University of Medicine and Dentistry of New Jersey, and Rutgers School of Dental Medicine, Rutgers Health, Rutgers – The State University of New Jersey Contact Scott R Diehl, PhD, scott.diehl@rutgers.edu , 973-972-7053

  PublisherOA PDFDOI

• Data from Prognostic Utility of Anti-EBV Antibody Testing for Defining NPC Risk among Individuals from High-Risk NPC Families

  2023-03-31

  preprintOpen access

  <div>Abstract<p><b>Purpose:</b> Epstein–Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families.</p><p><b>Experimental Design:</b> We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/specificity and receiver operating characteristic (ROC) curves were calculated.</p><p><b>Results:</b> A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4–16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5–61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker.</p><p><b>Conclusions:</b> Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity. <i>Clin Cancer Res; 17(7); 1906–14. ©2011 AACR</i>.</p></div>

  PublisherDOI

• Genetics of musculoskeletal (TMD) and neuropathic orofacial pain: a narrative review

  Frontiers of Oral and Maxillofacial Medicine · 2023-03-01 · 1 citations

  reviewOpen access

  Background and Objective: Orofacial pain is a debilitating condition affecting individuals’ quality of life. Differences in pain perception and analgesia have been reported between individuals, suggesting genetics as a contributing factor. This genetic component of orofacial pain can be best defined as complex due to contributions from multiple genes, which interact with each other and additional environmental factors. The objective of this review was to provide a summary of the progress made in the field of musculoskeletal [temporomandibular disorders (TMD)] and neuropathic orofacial pain genetics. Methods: PubMed database was searched using the following Medical Subject Headings: (("Facial Pain/genetics"[Mesh]) OR ("Trigeminal Neuralgia/genetics"[Mesh]) OR ("Trigeminal Nerve Diseases/genetics"[Mesh]) OR (“Temporomandibular Joint Disorders/genetics"[Mesh])). The search was limited to publications in English. No time-frame restriction was used. Key Content and Findings: In this review, we discuss progress made in the field of orofacial pain genetics with the focus on non-malignant and non-odontogenic musculoskeletal, i.e., TMDs and forms of trigeminal neuropathic pain including post-traumatic trigeminal neuropathic pain (PTTN) and trigeminal neuralgia (TN). Available evidence supports the role of genetics in orofacial pain with variations in voltage gated ion channels, transient receptor potential channels, and GABA receptor-binding genes possessing the strongest support. Conclusions: For most cases, orofacial pain conditions such as TMDs, TN, and PTTN follow a complex multifactorial pattern of inheritance with multiple compounding environmental and genetic factors. Under such conditions, the effect of individual genetic variation is modest. Defining the implications of individual genetic factors would thus require large samples of hundreds or thousands of carefully diagnosed patients and well-matched controls to provide sufficient statistical power. Rare damaging mutations that have a major effect on risk probably account for a small portion of cases due to aggregation in families, but nonetheless may be valuable for identifying pathophysiological mechanisms. Overall, the current evidence strongly suggests that inherited genetic differences among individuals make an important contribution to the development and severity of pain in conditions such as TMDs, TN, and PTTN. Future research should be aimed at identifying both the common variants with modest effects and rare damaging mutations with large effects on increasing patient risk. Such findings would offer promising avenues for development of novel therapeutic approaches to improve treatment for patients suffering from these debilitating conditions.

  PublisherDOI

• Data from Prognostic Utility of Anti-EBV Antibody Testing for Defining NPC Risk among Individuals from High-Risk NPC Families

  2023-03-31

  preprintOpen access

  <div>Abstract<p><b>Purpose:</b> Epstein–Barr virus (EBV) infection and a family history of nasopharyngeal carcinoma (NPC) are associated with NPC risk. We examined the risk associated with EBV markers and their clinical utility to identify NPC susceptibles within high-risk NPC families.</p><p><b>Experimental Design:</b> We evaluated antibody titers against viral capsid antigen (VCA) IgA, EBV nuclear antigen-1 (EBNA1) IgA, and DNase among unaffected relatives of NPC cases from 358 multiplex families in Taiwan. Incident NPC cases were identified via linkage to the National Cancer Registry. Clinical examinations of 924 individuals were also done to identify occult, asymptomatic NPC. Baseline EBV serology was used to estimate NPC risk using rate ratios with 95% CI. Associated sensitivity/specificity and receiver operating characteristic (ROC) curves were calculated.</p><p><b>Results:</b> A total of 2,444 unaffected individuals with 15,519 person-years (6.5 years median follow-up) yielded 14 incident NPC cases (nearly 11 times the general population rate). The absolute rate of NPC among anti-EBV EBNA1 IgA seropositives using a standard positivity cutoff versus an optimized cutoff point defined by ROC analyses was 265/100,000 person-years with a 4.7-fold increased risk of NPC (95% CI: 1.4–16) and 166/100,000 person-years with a 6.6-fold increase (95% CI: 1.5–61), respectively. Sensitivity and specificity using the optimized positivity cutoff points were 85.7% and 51.2%, respectively. It is estimated that active evaluation of 49% of individuals from high-risk NPC families seropositive for this marker could lead to earlier detection of up to 86% of NPC cases. Risks associated with the other three EBV markers were weaker.</p><p><b>Conclusions:</b> Future efforts are needed to identify susceptibility markers among high-risk NPC families that maximize both sensitivity and specificity. <i>Clin Cancer Res; 17(7); 1906–14. ©2011 AACR</i>.</p></div>

  PublisherDOI

• Supplementary Tables S1-S2 from Prognostic Utility of Anti-EBV Antibody Testing for Defining NPC Risk among Individuals from High-Risk NPC Families

  2023-03-31

  supplementary-materialsOpen access

  <p>Supplementary Tables S1-S2.</p>

  PublisherOA PDFDOI

• Supplementary Tables S1-S2 from Prognostic Utility of Anti-EBV Antibody Testing for Defining NPC Risk among Individuals from High-Risk NPC Families

  2023-03-31

  supplementary-materialsOpen access

  <p>Supplementary Tables S1-S2.</p>

  PublisherDOI

• Follow‐up study of veterans with white and red oral mucosal lesions at Veterans Affairs Dental Clinics

  Clinical and Experimental Dental Research · 2022 · 2 citations

  • Medicine
  • Dermatology
  • Internal medicine

  OBJECTIVES: This analysis examined the clinical and histopathological characteristics of white and red oral mucosal lesions and patient lifestyle behaviors to understand how the lesions changed over 19-23 years, including among patients who developed oral and pharyngeal cancer. MATERIALS AND METHODS: Seventy-five individuals with red and/or white oral mucosal lesions with clinical diagnoses of smokeless tobacco lesions, leukoplakia, erythroplakia, lichen planus, ulcer, and virus-associated lesions were identified in six Veterans Affairs Medical Center Dental Clinics (VAMC) from 1996 to 2001. Biopsy results and patients' sociodemographic, medical, and tobacco/alcohol use characteristics were obtained. Study dentists used standardized forms to capture information about the lesions. Study participants were re-examined at intervals through January 2002. In 2020, a retrospective review of VAMC and public records ascertained whether participants developed oral cancer or died. RESULTS: The most common red or white oral mucosal lesions among the 75 study participants were leukoplakia (36.0%), smokeless tobacco lesions (26.7%), virus-associated lesions (18.7%), and lichen planus (16.0%). Lesions in 11% of participants with leukoplakia and one-third of participants with lichen planus persisted for 5 years or more. Dysplasia was present in four participants with leukoplakia. Seventeen percent of participants developed a new white or red oral mucosal lesion. Five patients (6.1%) developed oral or pharyngeal cancer, four among participants with leukoplakia (one with prior dysplasia) and one among participants with lichen planus. Four of the cancers developed 6-20 years after enrollment, and only one was at the original lesion site. CONCLUSIONS: The occurrence of oral and pharyngeal cancers in some study participants with white and red oral mucosal lesions many years after enrollment reinforces the need for patients, dentists, and health care systems to have better methods to identify and assess the malignant potential of oral lesions, monitor patients over time, and intercept high-risk oral lesions before they become cancerous.

  PublisherDOI

Recent grants

• NIH Grant R01DE016057

  NIH · $1.8M · 2010

• NIH Grant R01MH045390

  NIH · $4.4M · 2001

• NIH Grant R01DC000038

  NIH · $1.6M · 1997

Frequent coauthors

• Alisa M. Goldstein

  National Cancer Institute

  50 shared

• Allan Hildesheim

  Instituto Costarricense de Investigación y Enseñanza en Nutrición y Salud

  50 shared

• Kelly J. Yu

  40 shared

• Ruth M. Pfeiffer

  National Cancer Institute

  35 shared

• Athanasios I. Zavras

  Tufts University

  32 shared

• Pei‐Jen Lou

  National Taiwan University Hospital

  32 shared

• George Laskaris

  National and Kapodistrian University of Athens

  32 shared

• Chien‐Jen Chen

  Genomics Research Center, Academia Sinica

  31 shared

Labs

• Rutgers School of Dental Medicine - Oral BiologyPI