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1. Targeted Proteomic Quantitation of NRF2 Signaling and Predictive Biomarkers in HNSCC

Author

Wamsley, Nathan T., Wilkerson, Emily M., Guan, Li, LaPak, Kyle M., Schrank, Travis P., Holmes, Brittany J., Sprung, Robert W., Gilmore, Petra Erdmann, Gerndt, Sophie P., Jackson, Ryan S., Paniello, Randal C., Pipkorn, Patrik, Puram, Sidharth V., Rich, Jason T., Townsend, Reid R., Zevallos, José P., Zolkind, Paul, Le, Quynh-Thu, Goldfarb, Dennis, and Major, Michael B.

Published
2023
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2. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus–Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial

Author

Uppaluri, Ravindra, Campbell, Katie M, Egloff, Ann Marie, Zolkind, Paul, Skidmore, Zachary L, Nussenbaum, Brian, Paniello, Randal C, Rich, Jason T, Jackson, Ryan, Pipkorn, Patrik, Michel, Loren S, Ley, Jessica, Oppelt, Peter, Dunn, Gavin P, Barnell, Erica K, Spies, Nicholas C, Lin, Tianxiang, Li, Tiantian, Mulder, David T, Hanna, Youstina, Cirlan, Iulia, Pugh, Trevor J, Mudianto, Tenny, Riley, Rachel, Zhou, Liye, Jo, Vickie Y, Stachler, Matthew D, Hanna, Glenn J, Kass, Jason, Haddad, Robert, Schoenfeld, Jonathan D, Gjini, Evisa, Lako, Ana, Thorstad, Wade, Gay, Hiram A, Daly, Mackenzie, Rodig, Scott J, Hagemann, Ian S, Kallogjeri, Dorina, Piccirillo, Jay F, Chernock, Rebecca D, Griffith, Malachi, Griffith, Obi L, and Adkins, Douglas R

Subjects
Clinical Research, Sexually Transmitted Infections, Patient Safety, Infectious Diseases, Cancer, Dental/Oral and Craniofacial Disease, Rare Diseases, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, B7-H1 Antigen, Chemotherapy, Adjuvant, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Interferon-gamma, Lymphocytes, Tumor-Infiltrating, Male, Middle Aged, Neoadjuvant Therapy, Neoplasm Recurrence, Local, Papillomaviridae, Squamous Cell Carcinoma of Head and Neck, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposePembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.Patients and methodsNeoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (

Published
2020

4. Immune Cell Deconvolution Reveals Possible Association of γδ T Cells with Poor Survival in Head and Neck Squamous Cell Carcinoma

Author

Parikh, Anuraag S., primary, Li, Yize, additional, Mazul, Angela, additional, Yu, Victoria X., additional, Thorstad, Wade, additional, Rich, Jason, additional, Paniello, Randal C., additional, Caruana, Salvatore M., additional, Troob, Scott H., additional, Jackson, Ryan S., additional, Pipkorn, Patrik, additional, Zolkind, Paul, additional, Qi, Zongtai, additional, Adkins, Douglas, additional, Ding, Li, additional, and Puram, Sidharth V., additional

Published
2023
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5. Abstract PO-012: Spatial transcriptomic analysis of HPV-related and HPV-unrelated head and neck squamous cell carcinoma

Author

Barrett, Thomas F., primary, Simkin, Dor, additional, Greenwald, Alissa R., additional, Parikh, Anuraag, additional, Gay, Hiram, additional, Apicelli, Anthony, additional, Adkins, Douglas, additional, Thorstad, Wade, additional, Rich, Jason T., additional, Paniello, Randal C., additional, Zolkind, Paul, additional, Pipkorn, Patrik, additional, Jackson, Ryan S., additional, Chernock, Rebecca, additional, Tirosh, Itay, additional, and Puram, Sidharth V., additional

Published
2023
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6. Memory-like Differentiation, Tumor-Targeting mAbs, and Chimeric Antigen Receptors Enhance Natural Killer Cell Responses to Head and Neck Cancer

Author

Jacobs, Miriam T., primary, Wong, Pamela, additional, Zhou, Alice Y., additional, Becker-Hapak, Michelle, additional, Marin, Nancy D., additional, Marsala, Lynne, additional, Foster, Mark, additional, Foltz, Jennifer A., additional, Cubitt, Celia C., additional, Tran, Jennifer, additional, Russler-Germain, David A., additional, Neal, Carly, additional, Kersting-Schadek, Samantha, additional, Chang, Lily, additional, Schappe, Timothy, additional, Pence, Patrick, additional, McClain, Ethan, additional, Zevallos, Jose P., additional, Rich, Jason T., additional, Paniello, Randal C., additional, Jackson, Ryan S., additional, Pipkorn, Patrik, additional, Adkins, Douglas R., additional, DeSelm, Carl J., additional, Berrien-Elliott, Melissa M., additional, Puram, Sidharth V., additional, and Fehniger, Todd A., additional

Published
2023
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7. Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma

Author

Puram, Sidharth V., Mints, Michael, Pal, Ananya, Qi, Zongtai, Reeb, Ashley, Gelev, Kyla, Barrett, Thomas F., Gerndt, Sophie, Liu, Ping, Parikh, Anuraag S., Ramadan, Salma, Law, Travis, Mroz, Edmund A., Rocco, James W., Adkins, Doug, Thorstad, Wade L., Gay, Hiram A., Ding, Li, Paniello, Randal C., Pipkorn, Patrik, Jackson, Ryan S., Wang, Xiaowei, Mazul, Angela, Chernock, Rebecca, Zevallos, Jose P., Silva-Fisher, Jessica, Tirosh, Itay, Puram, Sidharth V., Mints, Michael, Pal, Ananya, Qi, Zongtai, Reeb, Ashley, Gelev, Kyla, Barrett, Thomas F., Gerndt, Sophie, Liu, Ping, Parikh, Anuraag S., Ramadan, Salma, Law, Travis, Mroz, Edmund A., Rocco, James W., Adkins, Doug, Thorstad, Wade L., Gay, Hiram A., Ding, Li, Paniello, Randal C., Pipkorn, Patrik, Jackson, Ryan S., Wang, Xiaowei, Mazul, Angela, Chernock, Rebecca, Zevallos, Jose P., Silva-Fisher, Jessica, and Tirosh, Itay

Abstract

Head and neck squamous cell carcinoma (HNSCC) includes a subset of cancers driven by human papillomavirus (HPV). Here we use single-cell RNA-seq to profile both HPV-positive and HPV-negative oropharyngeal tumors, uncovering a high level of cellular diversity within and between tumors. First, we detect diverse chromosomal aberrations within individual tumors, suggesting genomic instability and enabling the identification of malignant cells even at pathologically negative margins. Second, we uncover diversity with respect to HNSCC subtypes and other cellular states such as the cell cycle, senescence and epithelial-mesenchymal transitions. Third, we find heterogeneity in viral gene expression within HPV-positive tumors. HPV expression is lost or repressed in a subset of cells, which are associated with a decrease in HPV-associated cell cycle phenotypes, decreased response to treatment, increased invasion and poor prognosis. These findings suggest that HPV expression diversity must be considered during diagnosis and treatment of HPV-positive tumors, with important prognostic ramifications.

Published
2023
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9. Oromandibular Dystonia: A Clinical Examination of 2,020 Cases

Author

Scorr, Laura M., primary, Factor, Stewart A., additional, Parra, Sahyli Perez, additional, Kaye, Rachel, additional, Paniello, Randal C., additional, Norris, Scott A., additional, Perlmutter, Joel S., additional, Bäumer, Tobias, additional, Usnich, Tatiana, additional, Berman, Brian D., additional, Mailly, Marie, additional, Roze, Emmanuel, additional, Vidailhet, Marie, additional, Jankovic, Joseph, additional, LeDoux, Mark S., additional, Barbano, Richard, additional, Chang, Florence C. F., additional, Fung, Victor S. C., additional, Pirio Richardson, Sarah, additional, Blitzer, Andrew, additional, and Jinnah, H. A., additional

Published
2021
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10. Zinc isotopic evidence for the origin of the moon

Author

Paniello, Randal C., Day, James M.D., and Moynier, Frederic

Subjects
Zinc -- Research, Moon -- Observations, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Volatile elements have a fundamental role in the evolution of planets. But how budgets of volatiles were set in planets, and the nature and extent of volatile-depletion of planetary bodies [...]

Published
2012

11. Correction: Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus–unrelated Head and Neck Cancer: A Multicenter, Phase II Trial

Author

Uppaluri, Ravindra, primary, Campbell, Katie M., additional, Egloff, Ann Marie, additional, Zolkind, Paul, additional, Skidmore, Zachary L., additional, Nussenbaum, Brian, additional, Paniello, Randal C., additional, Rich, Jason T., additional, Jackson, Ryan, additional, Pipkorn, Patrik, additional, Michel, Loren S., additional, Ley, Jessica, additional, Oppelt, Peter, additional, Dunn, Gavin P., additional, Barnell, Erica K., additional, Spies, Nicholas C., additional, Lin, Tianxiang, additional, Li, Tiantian, additional, Mulder, David T., additional, Hanna, Youstina, additional, Cirlan, Iulia, additional, Pugh, Trevor J., additional, Mudianto, Tenny, additional, Riley, Rachel, additional, Zhou, Liye, additional, Jo, Vickie Y., additional, Stachler, Matthew D., additional, Hanna, Glenn J., additional, Kass, Jason, additional, Haddad, Robert, additional, Schoenfeld, Jonathan D., additional, Gjini, Evisa, additional, Lako, Ana, additional, Thorstad, Wade, additional, Gay, Hiram A., additional, Daly, Mackenzie, additional, Rodig, Scott J., additional, Hagemann, Ian S., additional, Kallogjeri, Dorina, additional, Piccirillo, Jay F., additional, Chernock, Rebecca D., additional, Griffith, Malachi, additional, Griffith, Obi L., additional, and Adkins, Douglas R., additional

Published
2021
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12. High-throughput mutational analysis of TOR1A in primary dystonia

Author

Truong Daniel D, Tarsy Daniel, Simon David K, Hedera Peter, Uitti Ryan J, Wszolek Zbigniew K, Batish Sat, Blitzer Andrew, Paniello Randal C, Karimi Morvarid, Tabbal Samer D, Racette Brad A, Perlmutter Joel S, Bastian Robert W, Xiao Jianfeng, Frei Karen P, Pfeiffer Ronald F, Gong Suzhen, Zhao Yu, and LeDoux Mark S

Subjects
Internal medicine, RC31-1245, Genetics, QH426-470
Abstract

Abstract Background Although the c.904_906delGAG mutation in Exon 5 of TOR1A typically manifests as early-onset generalized dystonia, DYT1 dystonia is genetically and clinically heterogeneous. Recently, another Exon 5 mutation (c.863G>A) has been associated with early-onset generalized dystonia and some ΔGAG mutation carriers present with late-onset focal dystonia. The aim of this study was to identify TOR1A Exon 5 mutations in a large cohort of subjects with mainly non-generalized primary dystonia. Methods High resolution melting (HRM) was used to examine the entire TOR1A Exon 5 coding sequence in 1014 subjects with primary dystonia (422 spasmodic dysphonia, 285 cervical dystonia, 67 blepharospasm, 41 writer's cramp, 16 oromandibular dystonia, 38 other primary focal dystonia, 112 segmental dystonia, 16 multifocal dystonia, and 17 generalized dystonia) and 250 controls (150 neurologically normal and 100 with other movement disorders). Diagnostic sensitivity and specificity were evaluated in an additional 8 subjects with known ΔGAG DYT1 dystonia and 88 subjects with ΔGAG-negative dystonia. Results HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG and c.863G>A mutations. Melting curves were normal in 250/250 controls and 1012/1014 subjects with primary dystonia. The two subjects with shifted melting curves were found to harbor the classic ΔGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset multifocal dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia. Conclusion First, HRM is an inexpensive, diagnostically sensitive and specific, high-throughput method for mutation discovery. Second, Exon 5 mutations in TOR1A are rarely associated with non-generalized primary dystonia.

Published
2009
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13. Synkinesis Following Recurrent Laryngeal Nerve Injury: A Computer Simulation

Author

Paniello, Randal C.

Subjects
Synkinesis, Recurrent Laryngeal Nerve Injuries, Computer Simulation, Article, Software
Abstract

When the recurrent laryngeal nerve (RLN) is injured, functional recovery may be limited by the number of axons that regrow across the site of injury, and by the proportions of these axons that reinnervate the antagonistic muscle (synkinesis). This process was investigated in a computer model of RLN recovery.Computer simulation.The developed computer program accepted as inputs: number of RLN axons; proportions of axons originally innervating adductor versus abductor, fraction of axons transected, fraction of axons that grow back, and width of 1 standard deviation about the mean. The program employed random sampling from a normal distribution to model various degrees of recovery, using random numbers to assign each axon to the correct muscle, an incorrect muscle, or no recovery. Each simulation was run 1,000×, and the mean, highest, and lowest degrees of synkinesis were determined.More severe injuries were associated with greater degrees of synkinesis. Extremes of synkinesis were possible but were rare. One example result, for a 50% injury with a 50% recovery rate, found: in the adductor muscles, 74.8% of axons will be innervated, of which 49.2% are the original uninjured axons, 19.4% are recovered adductor axons, and 6.2% are misdirected abductor axons. In the posterior cricoarytenoid (PCA), these values were 75.7%, 50.8%, 6.1%, and 18.8%, respectively. Results of many such simulations are plotted.Laryngeal synkinesis can be simulated based on known anatomic ratios and estimated recovery rates. The PCA is invariably much more affected by synkinetic reinnervation than are the adductor muscles.NA Laryngoscope, 126:1600-1605, 2016.

Published
2015

14. RECURRENT LARYNGEAL NERVE RECOVERY PATTERNS ASSESSED BY SERIAL ELECTROMYOGRAPHY

Author

Paniello, Randal C., Park, Andrea M., Bhatt, Neel, and Al-Lozi, Mohammed

Subjects
Time Factors, Laryngoscopy, Electromyography, Prognosis, Article, Nerve Regeneration, Disease Models, Animal, Random Allocation, Dogs, Recurrent Laryngeal Nerve Injuries, Animals, Female, Vocal Cord Paralysis, Follow-Up Studies
Abstract

Following acute injury to the recurrent laryngeal nerve (RLN), laryngeal electromyography (LEMG) is increasingly being used to determine prognosis for recovery. The LEMG findings change during the recovery process, but the timing of these changes is not well described. In this canine study, LEMGs were obtained serially following model RLN injuries.Animal Study.Thirty-six canine RLNs underwent crush (n = 6), complete transection with reanastomosis (n = 6), half-transection half-crush (n = 5), cautery (n = 5), stretch (n = 5), inferior crush (n = 4), or inferior transection with reanastomosis (n = 5) injuries. Injuries were performed 5 cm from cricoid or were 5 cm further inferior. Under light sedation, LEMG of thyroarytenoid muscles was performed monthly for 6 months following injury. At 6 months, spontaneous and induced vocal fold motion was assessed.Except for the stretch injury, the remaining groups showed very similar recovery patterns. Fibrillation potentials (FPs) and/or positive sharp waves (PSWs; signs of bad prognosis) were seen in all cases at 1 month and lasted on average for 2.26 months (range = 1-4 months). Motor unit potentials of at least 2+ (scale = 0-4+; signs of good prognosis) were seen beginning at 3.61 months (range = 2-6 months). The stretch injury was less severe, with 3 of 5 showing no FPs/PSWs at 1 month; all recovered full mobility. Ten of the 36 thyroarytenoid muscles (27.8%) had 1 electromyograph showing both bad prognosis and good prognosis signs simultaneously at 2 to 4 months postinjury.LEMG can be used to predict RNL recovery, but timing is important and LEMG results earlier than 3 months may overestimate a negative prognosis.NA Laryngoscope, 126:651-656, 2016.

Published
2015

16. Biomarker and Tumor Responses of Oral Cavity Squamous Cell Carcinoma to Trametinib: A Phase II Neoadjuvant Window-of-Opportunity Clinical Trial

Author

Uppaluri, Ravindra, primary, Winkler, Ashley E., additional, Lin, Tianxiang, additional, Law, Jonathan H., additional, Haughey, Bruce H., additional, Nussenbaum, Brian, additional, Paniello, Randal C., additional, Rich, Jason T., additional, Diaz, Jason A., additional, Michel, Loren P., additional, Wildes, Tanya, additional, Dunn, Gavin P., additional, Zolkind, Paul, additional, Kallogjeri, Dorina, additional, Piccirillo, Jay F., additional, Dehdashti, Farrokh, additional, Siegel, Barry A., additional, Chernock, Rebecca D., additional, Lewis, James S., additional, and Adkins, Douglas R., additional

Published
2017
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17. Laryngeal Adductor Function in Experimental Models of Recurrent Laryngeal Nerve Injury

Author

Paniello, Randal C., Rich, Jason T., and Debnath, Nick L.

Subjects
Disease Models, Animal, Dogs, Recurrent Laryngeal Nerve Injuries, Animals, Female, Recovery of Function, Laryngeal Muscles, Article
Abstract

Most patients with unilateral vocal fold paralysis experience some degree of spontaneous reinnervation, which depends upon the type and severity of recurrent laryngeal nerve (RLN) injury. After partial recovery, the paretic vocal fold may or may not adduct adequately to allow glottic closure, which in turn affects phonatory and swallowing outcomes. This process was studied in a series of canine laryngeal nerve injury models.Animal (canine) experiments.Maximum stimulable laryngeal adductor pressure (LAP) was measured pretreatment (baseline) and at 6 months following experimental RLN injuries (total n = 59). The nine study groups were designed to simulate a range of severities of RLN injury.The greatest LAP recovery, at 108% of original baseline, was seen in a 50% transection model; the least recovery was seen when the RLN underwent complete transection with repair, at 56% with precise alignment and 50% with alignment reversed. Intermediate models (partial RLN injuries) gave intermediate results. Crush models recovered 105% of LAP, whereas a half-transection, half-crush injury recovered 72%, and cautery injuries recovered 61%. Controls (complete transection without repair) had no measurable recovery.The injured RLN has a strong tendency to recover. Restoration of adductor strength, as determined by the LAP, was predictably related to the severity of RLN injury. The model RLN injuries studied provide a range of expected outcomes that can be used for future experiments exploring interventions that may improve postinjury adductor function.NA.

Published
2014

20. Nab‐paclitaxel‐based compared to docetaxel‐based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck

Author

Schell, Amy, primary, Ley, Jessica, additional, Wu, Ningying, additional, Trinkaus, Kathryn, additional, Wildes, Tanya Marya, additional, Michel, Loren, additional, Thorstad, Wade, additional, Gay, Hiram, additional, Lewis, James, additional, Rich, Jason, additional, Diaz, Jason, additional, Paniello, Randal C., additional, Nussenbaum, Brian, additional, and Adkins, Douglas R., additional

Published
2015
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21. A rare sequence variant in intron 1 of THAP1 is associated with primary dystonia

Author

Vemula, Satya R., primary, Xiao, Jianfeng, additional, Zhao, Yu, additional, Bastian, Robert W., additional, Perlmutter, Joel S., additional, Racette, Brad A., additional, Paniello, Randal C., additional, Wszolek, Zbigniew K., additional, Uitti, Ryan J., additional, Van Gerpen, Jay A., additional, Hedera, Peter, additional, Truong, Daniel D., additional, Blitzer, Andrew, additional, Rudzińska, Monika, additional, Momčilović, Dragana, additional, Jinnah, Hyder A., additional, Frei, Karen, additional, Pfeiffer, Ronald F., additional, and LeDoux, Mark S., additional

Published
2014
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23. High-throughput mutational analysis of TOR1A in primary dystonia

Author

Xiao, Jianfeng, primary, Bastian, Robert W, additional, Perlmutter, Joel S, additional, Racette, Brad A, additional, Tabbal, Samer D, additional, Karimi, Morvarid, additional, Paniello, Randal C, additional, Blitzer, Andrew, additional, Batish, Sat Dev, additional, Wszolek, Zbigniew K, additional, Uitti, Ryan J, additional, Hedera, Peter, additional, Simon, David K, additional, Tarsy, Daniel, additional, Truong, Daniel D, additional, Frei, Karen P, additional, Pfeiffer, Ronald F, additional, Gong, Suzhen, additional, Zhao, Yu, additional, and LeDoux, Mark S, additional

Published
2009
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24. High-throughput mutational analysis of TOR1A in primary dystonia.

Author

Jianfeng Xiao, Bastian, Robert W., Perlmutter, Joel S., Racette, Brad A., Tabbal, Samer D., Karimi, Morvarid, Paniello, Randal C., Blitzer, Andrew, Batish, Sat Dev, Wszolek, Zbigniew K., Uitti, Ryan J., Hedera, Peter, Simon, David K., Tarsy, Daniel, Truong, Daniel D., Frei, Karen P., Pfeiffer, Ronald F., Suzhen Gong, Yu Zhao, and LeDoux, Mark S.

Subjects
DYSTONIA, EXONS (Genetics), CAUCASIAN race, MOVEMENT disorders, GENETIC disorders
Abstract

Background: Although the c.904_906delGAG mutation in Exon 5 of TOR1A typically manifests as early-onset generalized dystonia, DYT1 dystonia is genetically and clinically heterogeneous. Recently, another Exon 5 mutation (c.863G>A) has been associated with early-onset generalized dystonia and some ΔGAG mutation carriers present with late-onset focal dystonia. The aim of this study was to identify TOR1A Exon 5 mutations in a large cohort of subjects with mainly non-generalized primary dystonia. Methods: High resolution melting (HRM) was used to examine the entire TOR1A Exon 5 coding sequence in 1014 subjects with primary dystonia (422 spasmodic dysphonia, 285 cervical dystonia, 67 blepharospasm, 41 writer's cramp, 16 oromandibular dystonia, 38 other primary focal dystonia, 112 segmental dystonia, 16 multifocal dystonia, and 17 generalized dystonia) and 250 controls (150 neurologically normal and 100 with other movement disorders). Diagnostic sensitivity and specificity were evaluated in an additional 8 subjects with known ΔGAG DYT1 dystonia and 88 subjects with ΔGAG-negative dystonia. Results: HRM of TOR1A Exon 5 showed high (100%) diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG and c.863G>A mutations. Melting curves were normal in 250/250 controls and 1012/1014 subjects with primary dystonia. The two subjects with shifted melting curves were found to harbor the classic ΔGAG deletion: 1) a non-Jewish Caucasian female with childhood-onset multifocal dystonia and 2) an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia. Conclusion: First, HRM is an inexpensive, diagnostically sensitive and specific, high-throughput method for mutation discovery. Second, Exon 5 mutations in TOR1A are rarely associated with non-generalized primary dystonia. [ABSTRACT FROM AUTHOR]

Published
2009
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