Oral squamous cell cancer (OSCC) is the sixth most common cancer worldwide and accounts for 2% of all malignancies in the USA. In this year alone, 40,000 men and women will develop OSCC, and unfortunately, only two-thirds of these OSCC patients will survive more than five years. While the past decades have seen advances in ablative/reconstructive surgery, radiation therapy, and chemotherapy, the overall survival rate of OSCC patients has not improved significantly, and there are multiple co-morbidities which arise from treatment which may negatively affect quality of life. Thus, there is a real need for innovative new approaches to treating oral squamous cell cancer.
Immunotherapy has arisen as a novel treatment modality for several cancers, and biomaterials-based cancer immunotherapy platforms are currently being developed in our laboratory. Our goal is to evaluate these promising technologies for use in oral squamous cell carcinoma. The overall hypothesis is that biomaterials-based constructs able to provide appropriate spatiotemporal presentation of bioactive factors to key immune cells can induce anti-tumor immunity.
The focus of our current research is to develop novel material-based immunotherapies for the treatment of head and neck cancer and explore mechanisms of how this approach may synergize with other modalities of treatment such as chemo/radiation therapy. The paradigm of in situ cell programming using biomaterials is also being utilized in a separate research project in collaboration with MIT, exploring the use of layer-by-layer technology to deliver bioactive factors for the enhancement of craniofacial bone regeneration.
We are currently working to characterize a new preclinical mouse models of OSCC, determine the effectiveness of implantable cancer immunotherapies for treating OSCC, and to explore any synergistic effects that arise by combining these materials with other immunotherapeutic strategies.
Overall, these studies are anticipated to enhance our understanding of the role dendritic cells and tumor-specific cytotoxic T cells play in the treatment of OSCC, and may also contribute to the development of novel immunotherapies for OSCC.
Bone fractures are challenging to heal because of the sudden loss of bone and vasculature. Current treatments are inadequate because metal-based devices for bone fixation and biopolymer-based devices for bone regeneration do not stimulate rapid bone formation once implanted or produce weak or improperly healed bone. This inability to rapidly repair the large volume of lost bone and vasculature after trauma leads to increased reactive oxygen species (ROS) and oxidative stress at the fracture site, which impedes normal bone healing. Our long-term goal is to develop clinically useful, regenerative devices that accelerate bone healing.
Our objectives for this proposal are to (1) uncover material properties that reduce ROS and enhance antioxidant, osteogenic, and angiogenic capacity and (2) develop novel nano-scale surface chemistries and 3D architectures that are fabricated for fixative and resorbable devices that stimulate rapid biomineral and vascular formation in fracture sites. We will develop 3D nanofabrication and printing methods to create new amorphous silicon oxynitrophosphide (SiONPx) based devices that provide structural and antioxidant support for rapid bone healing via release of ionic Si and rapid formation of a surface hydroxyapatite layer for bone attachment, respectively. Our central innovation is the development of a new class of implantable devices that can potentially adapt to the challenging oxidative environment within a bony defect. Once such devices become clinically available, there is the promise that a significant advance will have been made toward translation of these devices and fabrication methods in patients needing rapid healing of fractures. These results will have a positive impact in supporting future clinical trials of new antioxidant materials on biomedical devices that can reduce patient healing time, reduce medical care cost, and increase the quality of newly formed bone in traumatic fractures.
Venu Varanasi (UT Arlington, PI)
Kamal Awad, PhD
Audra Boehm, DDS, MD, MA
Neeraja Dharmaraj, PhD
Bristol Galbraith, DDS
Nourhan Hussein, BDS, MS
James Park, DDS
NIDCR, Grant # R56 DE027964 and R01 DE031872
Osteo Science Foundation, Peter Geistlich Research Award
KLS Martin Group
Awad K, Ahuja N, Young S, Brotto M, Varanasi V: Bioactive Silicon Oxynitride Coatings and Innovative Nanoparticles as Next-Generation Biomaterials for Rapid Bone Regeneration. American Society for Bone and Mineral Research Annual Meeting, Austin, Texas (Sep 9-12, 2022).
Ahuja, N, Awad K, Yang S, Dong H, Brotto M, Aswath P, Young S, Varanasi V: Increasing N/O Ratio in Antioxidant SiONx Coatings Enhances Osteogenic Capacity. American Association for Dental, Oral, and Craniofacial Research Annual Meeting, Atlanta, Georgia (Mar 24-26, 2022).
Varanasi V, Awad K, Ahuja N, Young S, Brotto M, Prisby R, Zui P, Aswath P: Antioxidant Nanocomposite Hydrogels for Rapid Critical Sized Bone Defect Healing. The American Society for Bone and Mineral Research Annual Meeting, San Diego, California (Oct 1-4, 2021).
Ahuja N, Awad K, Monte F, Brotto M, Aswath P, Kim H, Young S, Varanasi V: Effect of Silicon-Oxynitrophosphide on Osteogenesis and Angiogenesis in Craniofacial Applications. International Association of Dental Research Annual Meeting, Washington DC, USA (Mar 18-21, 2020).
Ahuja N, Awad K, Tran H, Wilson L, Aswath P, Young S, Varanasi V: Antioxidant Properties and Enhanced Osteointegration by SiONx Coated Mandibular Implants. International Association of Dental Research Annual Meeting, Vancouver, Canada (June 18-22, 2019).
Ahuja N, Awad K, Yang S, Dong H, Mikos AG, Aswath PB, Young S, Brotto M, Varanasi V: SiONx Coating Regulates Mesenchymal Stem Cell Antioxidant Capacity via NRF2 Activity Under Toxic Oxidative Stress Condition. Antioxidants (Basel), 13(2): 189, 2024.
wad K, Ahuja N, Yacoub AS, Brotto L, Young S, Mikos AG, Aswath P, Varanasi V: Revolutionizing Bone Regeneration: Advanced Biomaterials for Healing Compromised Bone Defects. Front Aging, 4:1217054, 2023.
Awad K, Young S, Aswath P, Varanasi V: Interfacial Adhesion and Surface Bioactivity of Anodized Titanium Modified with SiON and SiONP Surface Coatings. Surf Interfaces, 28:101645, 2022.
do Monte FA, Ahuja N, Awad K, Pan Z, Young S, Kim HKW, Aswath P, Brotto M, Varanasi VG: Silicon Oxynitrophosphide Nanoscale-Coating Enhances Antioxidant Marker -Induced Angiogenesis During In Vivo Cranial Bone Defect Healing. JBMR Plus, 5(4):e10425, 2021.
This proposal builds on our successes in developing a nanostructured material we call “MultiDomain Peptides” or MDPs. Amongst the many discoveries during our first funding period, we found that these hydrogels have remarkable properties in vivo, in particular: 1) The MDP amino acid sequence can be tailored for rapid or slow degradation. 2) The hydrogel is entirely infiltrated by host cells within 7 days where the large number of cells interacting with the MDP matrix provides for powerful and rapid response to the matrix. 3) No fibrous encapsulation is observed up to 42 days in vivo allowing for good communication between our nanostructured matrix and the biological system. 4) Biomimetic amino acid sequences can be added to the base MDP structure allowing it to provoke desired biological responses such as angiogenesis and neurogenesis. Published data from our previous funding period and unpublished preliminary data presented here demonstrate the extremely powerful angiogenic and neurogenic properties of carefully designed MDPs which is unprecedented elsewhere in the literature and is the basis for the current proposal. A key feature of our approach is that the MDP hydrogel is composed of just a single designed, synthetic peptide. There is no need for additional growth factors or cells, either of which increases the challenge of clinical translation due to unforeseen and undesirable biological responses such as immune reaction, host rejection or tumor formation. Our interdisciplinary team combines expertise in chemistry, materials science, nanotechnology, neuroscience and clinical medicine. We will generate data that will provide the framework for further advances in nanostructured tissue engineering generally as well as advances specific to neural regeneration.
Jeffrey Hartgerink, PhD (Rice University, PI)
Hyun-Kyoung Lee, PhD (co-I)
Andrew Bhagyam, DDS MD
NIDCR Grant #R01 DE021798
Sjogren’s Syndrome (SS) is a common auto-immune disease with a prevalence of 0.2 – 2.7% without a known cure. Lymphocytes infiltrate exocrine salivary and lacrimal glands to disrupt secretion leading to dry eye and/or mouth. SS affects a patient’s quality of life through difficulty swallowing, risks of dental caries, and often depression. Immune infiltrates primarily target secretory acinar cells leading to atrophy and decreased secretory output. T-cells were long believed to be the primary drivers of SS, but studies showed higher ratios of B-cells to T-cells in advanced disease stages. Additionally, the high prevalence of Th17 cells in glandular tissue and blood of patients with SS suggests an important role for T- helper cells and B-cells, but the mechanisms driving immune localization remain unknown. Much of our understanding of SS etiology comes from analysis of blood or salivary glands by flow cytometry. Although cytometry studies identified B and T lymphocyte subpopulations, a knowledge gap arises from the unmet need for an unbiased full immune profiling of glands affected by SS. Single-cell sequencing of the entire gland performing simultaneous whole transcriptome and variable diversity and joining genes (VDJ) analysis can identify the full repertoire of immune cell populations, including rare cells, and their clonality in SS salivary tissue. It also can map the true abundance of the Th17 population in individual patient samples and their relation to other immune cell types. Because the identification of the immune cell repertoire present in SS salivary glands does not provide information on the way they contribute subsequent loss of salivary function, it is critical to perform functional studies to assess the link between presence of these cells and loss of secretion. We will initiate these studies with Th17 cells, then expand them to other immune populations as they are identified by genomic sequencing.
We hypothesize that Th17 cells along with other yet unidentified immune cells contribute to the loss of salivary gland function by reducing the secretory capabilities and increasing cellular death of acinar cells. We will use single-cell RNA Sequencing to broadly profile the immune microenvironment of affected salivary glands in SS patients and then study the functional link between pathogenic immune cells and reduced secretory function using advanced 3D culture systems.
Mary C. Farach-Carson, PhD (co-PI)
Danielle Wu, PhD
Caitlynn Barrows, BS (PhD Graduate Student)
Oral & Maxillofacial Surgery Foundation, Research Support grant
Barrows C*, Wu D, Callahan LS, Young S, Farach-Carson MC: Neurointegration of Assembling Human Salivary Stem/Progenitor Cells Assists Neotissue Formation. International Association for Dental Research Annual Meeting, (July 21-24, 2021).
Barrows C*, Wu D, Callahan LS, Young S, Farach-Carson MC: Neuroprogenitor Cells Influence Human Salivary Microstructures in Bioactive Hydrogels. International Association of Dental Research Annual Meeting, Washington DC, USA (Mar 18-21, 2020).
Barrows CML, Wu D, Young S, Farach-Carson MC: Human Minor Salivary Glands: A Readily Available Source of Salivary Stem/Progenitor Cells for Regenerative Applications. In Epithelial Cell Culture. Methods in Molecular Biology, Volume 2749. (ed. Baratta M). New York, NY: Humana, 2024: 25-38.
Barrows CML, Wu D, Farach-Carson MC, Young S: Building a Functional Salivary Gland for Cell-Based Therapy: More than Secretory Epithelial Acini. Tissue Eng Part A, 26(23-24):1332-1348, 2020.
TL1 graduate student training grant to Caitlynn Barrows
Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer worldwide and almost 50,000 men and women will develop HNSCC this year in the US alone. Unfortunately, only two-thirds of these HNSCC patients will survive more than five years, a statistic that has not changed in decades despite advances in surgery, radiation therapy, and chemotherapy. Given the well-known co-morbidities and recurrence rates associated with conventional treatments, there is a real need for innovative new approaches to treating HNSCC. Cancer immunotherapy (such as FDA-approved immune checkpoint antibodies) has arisen as an exciting treatment modality for several advanced-stage cancers including HNSCC, with the potential to generate specific and durable anti-tumor responses, although typically only in about 15-20% of patients.
Recently, a new class of immunotherapeutics based on synthetic cyclic dinucleotides (CDN) have been found to produce strong anti-tumor responses in preclinical models through the Stimulator of Interferon Genes (STING) pathway. However, to date CDN monotherapy has shown minimal efficacy in preclinical models of HNSCC, requiring multiple-injections and concomitant administration of immune checkpoint antibodies targeting the PD-1/PD-L1 axis for tumor rejection. In response to this challenge, our lab has developed a novel peptide nanofiber hydrogel-based platform for intratumoral CDN delivery called “STINGel” which has shown impressive and surprising efficacy in a challenging murine model of HNSCC.
Our goal is to determine the underlying mechanisms driving STINGel effectiveness in HNSCC. The overall hypothesis of this proposal is that intratumoral injection of STINGel renders immunologically refractory tumors sensitive to immune-mediated killing through multiple mechanisms including: 1) Prolonged release of CDN, 2) STINGel-driven recruitment of critical antigen presenting cells (APCs) to the site of injection, and 3) enhanced Type-1 interferon (IFN) response in both tumor cells and APCs within the tumor microenvironment (TME). Overall, this work is anticipated to enhance our understanding of the mechanisms by which STINGel can reverse resistance to immunomodulatory monotherapy in solid tumors and provide insights into how the adverse tumor microenvironment can be rendered more susceptible to immunotherapy.
Jeffrey Hartgerink, PhD (Rice University, Co-I)
Andrew Sikora MD, PhD (MD Anderson Cancer Center, Co-I)
Neeraja Dharmaraj, PhD
Brett Pogostin, BS (PhD Graduate Student)
Joseph Swain, BS (PhD Graduate Student)
Andrea Hernandez Molina, BS (PhD Graduate Student)
Gemalene Sunga, BS (PhD Graduate Student)
NIDCR, Grant # R00 DE023577, The Use of Novel Implantable Cancer Vaccines for the Treatment of Oral Cancer
NIDCR, Grant # R21 DE027794, STINGel Immunotherapy for Treatment-Resistant Head and Neck Cancer
NIDCR, Grant # R01 DE030140, SynerGel: A Novel Tumor Microenvironment-Modulating Hydrogel for Local Immunotherapy
NIDCR, Research Supplement Grant # R01 DE030140-02S1, SynerGel: A Novel Tumor Microenvironment-Modulating Hydrogel for Local Immunotherapy (Recipient: Andrea Hernandez Molina)
UTHealth Center for Clinical Trials and Translational Sciences TL1 Program, Grant # TL1 TR003169, Combining Tumor Microenvironment-Modulating Hydrogels with Radiotherapy for Local Immunotherapy (Recipient: Gemalene Sunga)
Sunga G*, Hernandez A, Pogostin B, Dharmaraj N, Veeramachaneni R, Hartgerink JD, Sikora AG, Young S: A Preclinical Model to Study Mechanisms Impacted by Combination Biomaterial-Based Immunotherapy and Radiotherapy. The University of Texas Graduate School of Biomedical Sciences Student Research Day, Houston, Texas (June 22, 2023).
Devkota L*, Bhavane R, Badachhape AA, Veeramachaneni R, Menon R, Bhandari P, Ghaghada KB, Young S, Sikora AG, Annapragada AV: PEGylated Liposomal Doxorubicin Improves Oral Cancer Response to Radio- Immunotherapy. American Association for Cancer Research Annual Meeting, Orlando, Florida (April 18, 2023).
Hernandez A*, Dharmaraj N, Sunga G, Rangel R, Sikora AG, Young S: Establishing the ROC1 preclinical model of oral cancer to understand location- based differences in the tumor immune microenvironment. The University of Texas Graduate School of Biomedical Sciences Student Research Day, Houston, Texas (June 23, 2022).
Young S, Dharmaraj N, Leach DG, Sikora AG, Hartgerink JD: Novel Tumor Microenvironment-Modulating Hydrogels for Cancer Immunotherapy. American Academy of Craniomaxillofacial Surgeons Annual Meeting, Orlando, Florida (Sep 2-5, 2021).
Leach D, Munoz N, Dupuis C, Williams M, Dixon K, Young S, Sheth R*, Hartgerink J: Self-assembling hydrogel platform improves intratumoral drug delivery and retention. Society of Interventional Radiology Annual Scientific Meeting, Seattle, Washington (Mar 28-Apr 2, 2020).
Yee A*, Dharmaraj N, Young S: IFN-I Pathway Gene Expression in MOC1 Cells Treated with CDN. International Association of Dental Research Annual Meeting, Washington DC, USA (Mar 18-21, 2020). (Conference cancelled)
Young S*, Dharmaraj N, Leach DG, Piotrowski S, Sikora AG, Hartgerink JD: Biomaterials-Based Cancer Immunotherapy in Preclinical Models of Treatment-Resistant Head and Neck Cancer. American Association of Oral & Maxillofacial Surgeons Annual Meeting, Boston, Massachusetts (September 16-21, 2019). (Winner, oral abstract session).
Leach DG*, Dharmaraj N, Piotrowski SL, Lopez-Silva TL, Lei YL, Sikora AG, Young S, Hartgerink JD: STINGel: A Biomaterial-Based Drug Delivery Vehicle for Enhanced Cancer Immunotherapy. Materials Research Society Spring Meeting, Phoenix, Arizona (April 22-26, 2019).
Young S*, Dharmaraj N, Leach DG, Piotrowski S, Sikora AG, Hartgerink JD: Biomaterials-Based Cancer Immunotherapy in Preclinical Models of Treatment-Resistant Head and Neck Cancer. American Association of Oral & Maxillofacial Surgeons Annual Meeting, Chicago, Illinois (October 8-13, 2018). (Winner, oral abstract session).
Couey M*, Dharmaraj N, Piotrowski SL, Golfman LS, Koshy ST, Li WA, Mooney DJ, Sikora AG, Young S: Robust Anti-Tumor Immunity Induced by Ectopic Expression of Viral Antigen is Transient and Limited by Immune Escape. UTHealth House Staff Research Day, Houston, Texas (April 9, 2018).
Dharmaraj, N*, Leach DG, Piotrowski SL, Sikora AG, Hartgerink JD, Young S: STINGel Immunotherapy in MOC2-E6E7, a Murine Orthotopic Model of HNSCC. J Dent Res, 97 (Spec Iss A):0722, 2018.
Dharmaraj N*, Piotrowski SL, Golfman LS, Koshy ST, Li WA, Mooney DJ, Sikora AG, Young S: Robust Anti-Tumor Immunity Induced by Ectopic Expression of Viral Antigen is Transient and Limited by Immune Escape. Innovations in Cancer Prevention and Research Conference Annual Meeting, Austin, Texas (November 13-14, 2017).
Young S*, Dharmaraj N, Piotrowski S, Koshy ST, Li WA, Mooney DJ, Sikora AG: Overcoming Resistance to Checkpoint Inhibitors through a Rationally-Designed Combinatorial Immunotherapy Approach. J Oral Maxillofac Surg,75(10 Suppl): e331-e332, 2017.
Sunga GM, Hartgerink JD, Sikora AG, Young S: Enhancement of Immunotherapies in Head and Neck Cancers Using Biomaterial-Based Treatment Strategies. Tissue Eng Part C Methods, 29(6): 257-275, 2023.
Hernandez A, Hartgerink JD, Young S: Self-assembling peptides as immunomodulatory biomaterials. Front Bioeng Biotechnol, 11:1139782, 2023.
Shi Y, Xie T, Leach DG, Wang B, Young S, Osman AA, Sikora AG, Ren X, Hartgerink JD, Myers JN, Rangel R: Local Anti-PD1 Delivery Prevents Progression of Premalignant Lesions in a 4NQO-Oral Carcinogenesis Mouse Model. Cancer Prev Res (Phila), 14(8):767-778, 2021.
Munoz N, Williams M, Dixon K, Dupuis C, McWatters A, Avritscher R, Manrique SZ, McHugh K, Murthy R, Tam A, Naing A, Patel S, Leach D, Hartgerink J, Young S, Prakash P, Hwu P, Sheth RA: Influence of Injection Technique, Drug Formulation and Tumor Microenvironment on Intratumoral Immunotherapy Delivery and Efficacy. J Immunother Cancer, 9(2):e001800, 2021.
Leach DG, Dharmaraj N, Lopez-Silva T, Rodriguez Venzor J, Pogostin B, Sikora AG, Hartgerink JD, Young S: Biomaterial-facilitated Immunotherapy for Established Oral Cancers. ACS Biomater Sci Eng, 7(2):415-421, 2021.
Leach DG, Newton JM, Florez M, Lopez-Silva T, Jones A, Young S, Sikora AG, Hargerink JD: Drug-Mimicking Nanofibrous Peptide Hydrogel for Inhibition of Inducible Nitric Oxide Synthase. ACS Biomater Sci Eng, 5(12):6755-65, 2019.
Newton JM, Hanoteau A, Liu HC, Gaspero A, Parikh F, Gartrell-Corrado RD, Hart TD, Laoui D, van Ginderachter JA, Dharmaraj N, Spanos WC, Saenger Y, Young S, and Sikora AG: Immune Microenvironment Modulation Unmasks Therapeutic Benefit of Radiotherapy and Checkpoint Inhibition. J Immunother Cancer, 7(1):216, 2019.
Dharmaraj N, Piotrowski SL, Huang C, Newton JM, Golfman LS, Hanoteau A, Koshy ST, Li WA, Pulikkathara MX, Zhang B, Burks JK, Mooney DJ, Lei YL, Sikora AG, Young S: Anti-Tumor Immunity Induced by Ectopic Expression of Viral Antigens is Transient and Limited by Immune Escape. Oncoimmunology, 8(4):e1568809, 2019.
Leach DG, Young S, Hartgerink JD: Advances in Immunotherapy Delivery from Implantable and Injectable Biomaterials. Acta Biomater, 88:15-31,2019.
Leach DG, Dharmaraj N, Piotrowski SL, Lopez-Silva TL, Lei YL, Young S*, Hartgerink JD*: STINGel: Controlled Release of a Cyclic Dinucleotide for Enhanced Cancer Immunotherapy. Biomaterials,163:67-75, 2018.
Hartgerink JD, Sikora AG, Leach DG, Newton JM, Young S. Synthetic Multidomain Peptide Biomaterials that Inhibit Inducible Nitric Oxide Synthase. US Patent Application # 62/950,718 (filed December 19, 2019). Pending.
Young S, Leach D, and Hartgerink JD. Hydrogel delivery of STING immunotherapy for treatment of cancer. US Patent Application # 62/520,834 (filed June 2017). Pending.
Although a wide range of animal models have been employed for the evaluation of bone tissue engineering technologies, they generally involve evaluation of tissue regeneration in an optimized wound bed (e.g., an aseptic, surgically-created bony defect in a healthy soft tissue envelope). However, such optimized bony defects do not adequately reflect the complexity of the wound bed in which regenerative therapies generally will be applied clinically, such as contaminated traumatic defects, post-radiation resection sites, or multiply- operated sites.
Accordingly, a tremendous need exists for the development of a pre-clinical animal model that suitably replicates the challenging compromised wound environment encountered in clinical scenarios (1) to guide our collective understanding of the mechanisms underlying the challenges to tissue regeneration in the compromised wound and (2) to facilitate rigorous pre-clinical evaluation of regenerative therapies to overcome the challenges of compromised maxillofacial defects.
We seek to build upon our established rabbit mandibular defect model to develop a new pre-clinical model of compromised maxillofacial wound healing for application as a clinically-relevant platform to meet these needs.
Kurt Kasper, PhD (co-PI)
Paulo Coelho, DDS, PhD (NYU, Co-PI)
Lukasz Witek, PhD (NYU, Co-PI)
Osteo Science Foundation, Peter Geistlich Research Award
Young S*, Piotrowski SL, Dharmaraj N, Clark A, Tailor R, Bankson J, Hill LR, Lai SY, Kasper FK: Development of a Novel Rabbit Model of Compromised Oral Wound Healing. American Academy of Craniomaxillofacial Surgeons Annual Meeting, San Antonio, Texas (May 9-10, 2019).
Kasper FK*, Piotrowski SL, Dharmaraj N, Clark A, Tailor R, Bankson J, Hill LR, Lai SY, Young S: Development of a Compromised Maxillofacial Wound Healing Model for Bone Tissue Engineering. TERMIS World Congress, Kyoto, Japan (September 4-7, 2018).
Piotrowski SL*, Dharmaraj N, Clark A, Tailor R, Bankson J, Hill LR, Lai SY, Kasper FK, Young S: Development of a Novel Pre-Clinical Model of Compromised Oral Wound Healing. J Dent Res, 97 (Spec Iss A):1510, 2018.
Wilson LA, Miller JJ, Work RK, Piotrowski SL, Young S, Lai SY, Lockworth CR, Hill LR: Novel Diet Regimen for Lagomorphs in a Compromised Oral Wound Healing Study. American Association for Laboratory Animal Science Annual Meeting, Austin, Texas (October 15-19, 2017).
Piotrowski SL, Wilson L, Maldonado KL, Tailor R, Hill LR, Bankson JA, Lai S, Kasper FK, Young S: Effect of Radiation on DCE-MRI Pharmacokinetic Parameters in a Rabbit Model of Compromised Maxillofacial Wound Healing: A Pilot Study. J Oral Maxillofac Surg, 78(6):1034.e1-1034.e10, 2020.
Shen C, Witek L, Flores R, Tovar N, Torroni A, Coelho PG, Kasper FK, Wong M, Young S: 3D Printing for Craniofacial Bone Tissue Engineering. Tissue Eng Part A, 26(23-24):1303-1311, 2020.
Piotrowski SL, Wilson L, Dharmaraj N, Hamze A, Clark A, Tailor R, Hill L, Lai S, Kasper K, and Young S: Development and Characterization of a Rabbit Model of Compromised Maxillofacial Wound Healing. Tissue Eng Part C Methods, 25(3):160-167, 2019.
Wilson LA, Miller JJ, Work RK, Piotrowski SL, Kasper FK, Young S, Lai SY, Lockworth CR, Hill LR: Novel Diet Regimen for Lagomorphs in a Compromised Oral Wound Healing Study. Lab Animal Sci Prof, Mar: 49-51, 2018.
Senior Research Scientist
Neeraja.Dharmaraj@uth.tmc.edu
713-486-4360
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GSBS Graduate Research Student
Caitlynn.Barrows@uth.tmc.edu
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Research Assistant II
Nourhan.I.Hussein@uth.tmc.edu
713-486-4360
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GSBS Graduate Research Student
Andrea.Hernandez@uth.tmc.edu
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GSBS Graduate Research student
gemalene.sunga@uth.tmc.edu
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Associate Professor
Simon.Young@uth.tmc.edu
713-486-2568
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Nguyen S*, Hernandez A, Sunga GM, Dharmaraj N, Young S: Analyzing the Tumor Immune Microenvironments of the ROC1 Oral Cavity and Flank Tumor Models with tSNE. The University of Texas Health Science Center at Houston School of Dentistry Student Research Showcase, Houston, Texas (October 31, 2023).
Sunga GM*, Hernandez A, Pogostin B, Dharmaraj N, Veeramachaneni R, Hartgerink JD, Sikora AG, Young S: A Fusion of Forces: A Preclinical Model to Study Mechanisms Impacted by Combination Biomaterial-Based Immunotherapy and Radiotherapy. The University of Texas Health Science Center at Houston School of Dentistry Student Research Showcase, Houston, Texas (October 31, 2023).
Hernandez A*, Sunga GM, Dharmaraj N, Hartgerink JD, Sikora AG, Young S: Comparing the ROC1 oral cavity model tumor immune microenvironment across time. The University of Texas Health Science Center at Houston School of Dentistry Student Research Showcase, Houston, Texas (October 31, 2023).
McGue C*, Aouizerat BE, Pearson AT, Thomas CM, Callahan NF, Morlandt AB, Young S, Melville JC, Shum JW, Viet CT: A Multi-modal Risk Score to Predict Progression of Oral Premalignant Lesions to Oral Squamous Cell Carcinoma. American Association of Oral & Maxillofacial Surgeons Annual Meeting, San Diego, California (September 20-23, 2023).
Nguyen ND*, Mah-Ginn K, Callahan NF, Morlandt AB, Cheng AC, Patel AA, Young S, Melville JC, Shum JW, Viet CT: A Multi-omic Biomarker of Mortality in Oral Squamous Cell Carcinoma. American Association of Oral & Maxillofacial Surgeons Annual Meeting, San Diego, California (September 20-23, 2023).
Neal TW*, Zuniga JR, Kim RY, Miloro M, Moles SLL, Petrisor D, Marwan HA, Young S, Melville JC, Hernandez-Nuno de la Rosa MFF: Does Immediate Long-span Nerve Allograft Affect the Incidence of Chronic Postsurgical and Neuropathic Pain in the Reconstructed Mandible Following Resection: An OMS Research Collaborative Project. American Association of Oral & Maxillofacial Surgeons Annual Meeting, San Diego, California (September 20-23, 2023).
Sunga G, Hernandez A, Pogostin B, Dharmaraj N, Veeramachaneni R, Hartgerink JD, Sikora AG, Young S: A Preclinical Model to Study Mechanisms Impacted by Combination Biomaterial-Based Immunotherapy and Radiotherapy. The University of Texas Graduate School of Biomedical Sciences Student Research Day, Houston, Texas (June 22, 2023).
Devkota L, Bhavane R, Badachhape AA, Veeramachaneni R, Menon R, Bhandari P, Ghaghada KB, Young S, Sikora AG, Annapragada AV: PEGylated Liposomal Doxorubicin Improves Oral Cancer Response to Radio- Immunotherapy. American Association for Cancer Research Annual Meeting, Orlando, Florida (April 18, 2023).
Yelick P, Lee SJ, Young S, Zhang W: New Strategies and Animal Models for Craniomaxillofacial Tissue Regeneration. TERMIS Asia-Pacific Congress, Jeju, South Korea (October 5-8, 2022).
Woernley T, Demian NM, Young S, Pearl CB, Wong ME: Comparison of Operating Room Time Length with the Use of Virtual Surgical Planning Versus Conventional Treatment of Mandible Fractures. Military Health System Research Symposium, Orlando, Florida (September 14, 2022).
McGue C, Asam KR, Yu G, Thomas CM, Callahan NF, Morlandt AB, Young S, Melville JC, Shum JW, Aouizerat BE, Viet CT: Epigenomic and Gene Expression Landscape of Tobacco Use in Oral Squamous Cell Carcinoma. American Association of Oral & Maxillofacial Surgeons Annual Meeting, New Orleans, Louisiana (September 12-17, 2022).
Boudreaux ER, Manon VA, Chubb D, Hanna I, Marchena J, Arribas AR, Young S, Wong ME, Melville JC: Implant Survival in Tissue-engineered Mandibular Reconstruction. American Association of Oral & Maxillofacial Surgeons Annual Meeting, New Orleans, Louisiana (September 12-17, 2022).
Awad K, Ahuja N, Young S, Brotto M, Varanasi V: Bioactive Silicon Oxynitride Coatings and Innovative Nanoparticles as Next-Generation Biomaterials for Rapid Bone Regeneration. American Society for Bone and Mineral Research Annual Meeting, Austin, Texas (Sep 9-12, 2022).
Hernandez A, Dharmaraj N, Sunga G, Rangel R, Sikora AG, Young S: Establishing the ROC1 preclinical model of oral cancer to understand location- based differences in the tumor immune microenvironment. The University of Texas Graduate School of Biomedical Sciences Student Research Day, Houston, Texas (June 23, 2022).
Melville JC, Manon VA, Young S, Arribas AR, Hanna I, Wong ME: In-Situ Tissue Engineering for the Reconstruction and Dental Rehabilitation of Severely Atrophic Mandibles: A Review of Technique. American Academy of Craniomaxillofacial Surgeons Annual Meeting, Jacksonville, Florida (Apr 22-23, 2022).
Manon VA, Oda N, Boudreaux E, Tran HQ, Young S, Melville JC: Implant Survival in Tissue-Engineered Mandibular Reconstruction – Early Experiences from the University of Texas Health Science Center at Houston. American Academy of Craniomaxillofacial Surgeons Annual Meeting, Jacksonville, Florida (Apr 22-23, 2022).
Barrows C, Wu D, Witt R, Callahan LS, Young S, Farach-Carson MC: Innervated Bioengineered Salivary Gland to Model SARS-CoV-2 Infectivity. American Association for Dental, Oral, and Craniofacial Research Annual Meeting, (Mar 24-26, 2022).
Ahuja, N, Awad K, Yang S, Dong H, Brotto M, Aswath P, Young S, Varanasi V: Increasing N/O Ratio in Antioxidant SiONx Coatings Enhances Osteogenic Capacity. American Association for Dental, Oral, and Craniofacial Research Annual Meeting, (Mar 24-26, 2022).
Zhang, W, Li Z, Saxena S, Fakhrzadeh A, Young S, Kohn J, Yelick P: Coordinated Bio?Engineered Alveolar Bone/Dental Implants For Repair Of Rabbit Mandible Critical Sized Defects. TERMIS World Congress, Maastricht, The Netherlands (November 15-19, 2021).
Mai S, Barrows C, Wu D, Young S, and Farach-Carson MC: Constructing a Tissue-Level Landscape of Potential Targets for SARS-CoV-2 Infection Through a Bioinformatic Analysis of Surrogate Markers. 26thHinman Student Research Symposium, Online (Oct 29-31, 2021).
Varanasi V, Awad K, Ahuja N, Young S, Brotto M, Prisby R, Zui P, Aswath P: Antioxidant Nanocomposite Hydrogels for Rapid Critical Sized Bone Defect Healing. The American Society for Bone and Mineral Research Annual Meeting, San Diego, California (Oct 1-4, 2021).
Young S, Dharmaraj N, Leach DG, Sikora AG, Hartgerink JD: Novel Tumor Microenvironment-Modulating Hydrogels for Cancer Immunotherapy. American Academy of Craniomaxillofacial Surgeons Annual Meeting, Orlando, Florida (Sep 2-5, 2021).
Melville JC, Young S, Farach L, Farach-Carson MC, Vigneswaran N, Manon V, Chubb D, Guenther J, Wong M: Genomic Analysis of COVID-Related Massive Macroglossia. American Academy of Craniomaxillofacial Surgeons Annual Meeting, Orlando, Florida (Sep 2-5, 2021).
Barrows C, Wu D, Callahan LS, Young S, Farach-Carson MC: Neurointegration of Assembling Human Salivary Stem/Progenitor Cells Assists Neotissue Formation. International Association for Dental Research Annual Meeting, (July 21-24, 2021).
Zhang W, Saxena S, Fakhrzadeh A, Rudolph S, Young S, Kohn J, Yelick PC: hDPSC/HUVEC seeded E1001(1k) constructs for craniomaxillofacial bone repair. International Association for Dental Research Annual Meeting, (July 21-24, 2021).
Agrawal N, Izumchenko E, Hodge K, Young S, Melville JC, Shum J, Alsuwied D, Sandulache V, Harris M, Manzi A, Goldberg M: A Phase II Study of PRV111 Nanoengineered Cisplatin Patch as a Neoadjuvant Therapy for Early-Stage Oral Squamous Cell Carcinoma (OSCC), Annual Meeting of the American Society of Clinical Oncology, Online (June 4-8, 2021).
Chow C, Young S, Wong ME, and Melville JC: Genomic Analysis of COVID-Related Massive Macroglossia, Annual Meeting of The Southwest Society of Oral & Maxillofacial Surgeons, San Antonio, Texas (April 17,2021).
Barrows CML*, Wu D, Callahan LS, Young S, Farach-Carson MC: Tissue Engineering Strategies to Develop a 3D Innervated Salivary Gland Avatar. 3rd Biennial Patricia Levy Zusman International Workshop on Neuroregeneration, Houston, Texas, USA (Mar 3-5, 2021).
Leach D, Munoz N, Dupuis C, Williams M, Dixon K, Young S, Sheth R*, Hartgerink J: Self-assembling hydrogel platform improves intratumoral drug delivery and retention. Society of Interventional Radiology Annual Scientific Meeting, Seattle, Washington (Mar 28-Apr 2, 2020).
Yee A, Dharmaraj N, Young S: IFN-I Pathway Gene Expression in MOC1 Cells Treated with CDN. International Association for Dental Research Annual Meeting, Washington DC, USA (Mar 18-21, 2020).
Ahuja N, Awad K, Monte F, Brotto M, Aswath P, Kim H, Young S, Varanasi V: Effect of Silicon-Oxynitrophosphide on Osteogenesis and Angiogenesis in Craniofacial Applications. International Association for Dental Research Annual Meeting, Washington DC, USA (Mar 18-21, 2020).
Leyva-Aranda V, Singh S, Telesforo MJ, Young S, Yee C, Hartgerink JD: Nanofibrous MultiDomain Peptide Hydrogels Provide T Cells a 3D, Cytocompatible Environment for Cell Expansion and Antigen-Specific Killing.ACS Biomater Sci Eng, in press. DOI: 10.1021/acsbiomaterials.3c01617.
Ahuja N, Awad K, Yang S, Dong H, Mikos AG, Aswath PB, Young S, Brotto M, Varanasi V: SiONx Coating Regulates Mesenchymal Stem Cell Antioxidant Capacity via NRF2 Activity Under Toxic Oxidative Stress Condition. Antioxidants (Basel), 13(2): 189, 2024.
Barrows CML, Wu D, Young S, Farach-Carson MC: Human Minor Salivary Glands: A Readily Available Source of Salivary Stem/Progenitor Cells for Regenerative Applications. In Epithelial Cell Culture. Methods in Molecular Biology, Volume 2749. (ed. Baratta M). New York, NY: Humana, 2024: 25-38.
Zuniga JR, Kim RY, Miloro M, Petrisor D, Marwan HA, Young S, Hernandez-Nuno de la Rosa MFF: Does Immediate Long-span Nerve Allograft Affect the Incidence of Chronic Postsurgical and Neuropathic Pain in the Reconstructed Mandible Following Resection for Benign and Malignany Disease: OMS Nerve Research Collaborative (OMSNRC). J Oral Maxillofac Surg, S0278-2391(23)01096-0, 2023.
Nayak VV, Slavin BV, Bergamo ETP, Torroni A, Runyan CM, Flores RL, Kasper FK, Young S, Coelho PG, Witek L: Three-Dimensional Printing Bioceramic Scaffolds Using Direct-Ink-Writing for Craniomaxillofacial Bone Regeneration. Tissue Eng Part C Methods, 29(7): 332-345, 2023.
Awad K, Ahuja N, Yacoub AS, Brotto L, Young S, Mikos AG, Aswath P, Varanasi V: Revolutionizing Bone Regeneration: Advanced Biomaterials for Healing Compromised Bone Defects. Front Aging, 4:1217054, 2023.
Sunga GM, Hartgerink JD, Sikora AG, Young S: Enhancement of Immunotherapies in Head and Neck Cancers Using Biomaterial-Based Treatment Strategies. Tissue Eng Part C Methods, 29(6): 257-275, 2023.
Melville JC, Rethman B, Kaleem A, Patel N, Marx RE, Tursun R, Shum J, Wong ME, and Young S: Tissue Engineering for Mandibular Reconstruction. Atlas Oral Maxillofac Surg Clin N Am, 31(2):165-176, 2023.
Hernandez A, Hartgerink JD, Young S: Self-assembling peptides as immunomodulatory biomaterials. Front Bioeng Biotechnol, 11:1139782, 2023.
Manon V, Oda N, Boudreaux E, Tran H, Young S, Melville JC: Implant Survival in Tissue-engineered Mandibular Reconstruction - Early Experiences. Craniomaxillofac Trauma Reconstr, 16(3):234-238, 2023.
Goldberg M, Manzi A, Birdi A, Laporte B, Conway, Cantin S, Mishra V, Singh A , Pearson AT, Goldberg ER, Goldberger S, Flaum B, Hasina R, London NR, Gallia GL, Bettegowda C, Young S, Sandulache V, Melville J, Shum J, O'Neill SE, Aydin E, Zhavoronkov A, Vidal A, Soto A, Alonso MJ, Rosenberg AJ, Lingen MW, D'Cruz A, Agrawal N, Izumchenko E: A nanoengineered topical transmucosal cisplatin delivery system induces anti-tumor response in animal models and patients with oral cancer. Nat Commun, 13(1):4829, 2022.
Manon V, Balandran S, Young S, Wong M, Melville JC: COVID-Associated Avascular Necrosis of the Maxilla – A Rare, New Side Effect of COVID-19. J Oral Maxillofac Surg, 80(7):1254-1259, 2022.
Hogan K, Smoak M, Koons G, Perez M, Bedell M, Jiang E, Young S, Mikos AG: Bioinspired electrospun dECM scaffolds promote muscle regeneration in a rat skeletal muscle defect model. J Biomed Mater Res A, 110(5):1090-1100, 2022.
Manon V, Chubb D, Farach LS, Farach-Carson M, Karam R, Vigneswaran N, Saluja K, Young S, Wong M, Melville JC: Massive macroglossia, a rare side effect of COVID-19: Clinical, histologic and genomic findings in COVID-19-positive versus -negative patients. Oral Maxillofac Surg, 26(4):613-618, 2022.
Awad K, Young S, Aswath P, Varanasi V: Interfacial Adhesion and Surface Bioactivity of Anodized Titanium Modified with SiON and SiONP Surface Coatings. Surf Interfaces, 28:101645, 2022.
Kaminagakura E, Tango RN, Cruz-Perez D, Bonan R, Yamamoto de Almeida L, Lanca ML, Bonan P, Martins H, Takahama A, Ito FA, Coutinho-Camillo C, Lourenco S, Caneppele T, Sikora AG, Kowalski LP, Young S: Oral Squamous Cell Carcinoma Outcome in Adolescent/Young Adult: Systematic Review and Meta-Analysis. Head Neck, 44(2):548-561, 2022.
Viet CT, Zhang X, Xu K, Yu G, Asam K, Thomas CM, Callahan NF, Doan C, Walker PC, Nguyen K, Kidd SC, Lee SC, Grandhi A, Allen CT, Young S, Melville JC, Shum JW, Viet DT, Herford AS, Roden DF, Gonzalez ML, Zhong JF, Aouizerat BE: Brush Swab as a Noninvasive Surrogate for Tissue Biopsies in Epigenomic Profiling of Oral Cancer. Biomark Res, 9(1):90, 2021.
Asghar S, Young S, Ansari A, Chapple A, Callahan N, Melville J, Kim R, Boehm A, Zaid W: The Incidence of COVID-19 Patients in Oral and Maxillofacial Surgery. J Oral Maxillofac Surg, S0278-2391(21)01126-5, 2021.
Shi Y, Xie T, Leach DG, Wang B, Young S, Osman AA, Sikora AG, Ren X, Hartgerink JD, Myers JN, Rangel R: Local Anti-PD1 Delivery Prevents Progression of Premalignant Lesions in a 4NQO-Oral Carcinogenesis Mouse Model. Caner Prev Res (Phila), 14(8): 767-778, 2021.
Saenthaveesuk P, Yang L, Zeng B, Xu M, Young S, Liao G, Liang Y: Development and Validation of Multiparametric MRI-based Nomogram for Predicting Occult Metastasis Risk in Early Tongue Squamous Cell Carcinoma. BMC Cancer, 21(1):408, 2021.
Munoz N, Williams M, Dixon K, Dupuis C, McWatters A, Avritscher R, Manrique SZ, McHugh K, Murthy R, Tam A, Naing A, Patel S, Leach D, Hartgerink J, Young S, Prakash P, Hwu P, Sheth RA: Influence of Injection Technique, Drug Formulation and Tumor Microenvironment on Intratumoral Immunotherapy Delivery and Efficacy. J Immunother Cancer, 9(2):e001800, 2021.
Leach DG, Dharmaraj N, Lopez-Silva T, Rodriguez Venzor J, Pogostin B, Sikora AG, Hartgerink JD, Young S: Biomaterial-facilitated Immunotherapy for Established Oral Cancers. ACS Biomater Sci Eng, 7(2):415-421, 2021.
do Monte F, Ahuja N, Awad K, Pan Z, Young S, Kim HKW, Aswath P, Brotto M, Varanasi VG: Silicon Oxynitrophosphide Nanoscale-Coating Enhances Antioxidant Marker -Induced Angiogenesis During In Vivo Cranial Bone Defect Healing. JBMR Plus, 5(4):e10425, 2021.
Shen C, Witek L, Flores R, Tovar N, Torroni A, Coelho PG, Kasper FK, Wong M, Young S: 3D Printing for Craniofacial Bone Tissue Engineering. Tissue Eng Part A, 26(23-24):1303-1311, 2020.
Barrows CML, Wu D, Farach-Carson MC, Young S: Building a Functional Salivary Gland for Cell-Based Therapy: More than Secretory Epithelial Acini. Tissue Eng Part A, 26(23-24):1332-1348, 2020.
Zhang W, Saxena S, Fakhrzadeh A, Rudolph S, Young S, Kohn J, Yelick PC: Use of Human Dental Pulp and Endothelial Cell Seeded Tyrosine-Derived Polycarbonate Scaffolds for Robust In Vivo Alveolar Jaw Bone Regeneration. Front Bioeng Biotechnol, 8:796, 2020. DOI: 10.3389/fbioe.2020.00796.
Piotrowski SL, Wilson L, Maldonado KL, Tailor R, Hill LR, Bankson JA, Lai S, Kasper FK, Young S: Effect of Radiation on DCE-MRI Pharmacokinetic Parameters in a Rabbit Model of Compromised Maxillofacial Wound Healing: A Pilot Study. J Oral Maxillofac Surg, 78(6):1034.e1-1034.e10, 2020.
Luo X, Donnelly CR, Gong W, Heath BR, Hao Y, Donnelly LA, Moghbell T, Tan YS, Lin X, Belle E, Kansy BA, Carey TE, Brenner JC, Cheng L, Polverini PJ, Morgan MA, Wen H, Prince ME, Ferris RL, Xie Y, Young S, Wolf GT, Chen Q, Lei YL: HPV16 Drives Cancer Immune Escape via NLRX1-mediated Degradation of STING. J Clin Invest, 130(4):1635-1652, 2020.
Melville JC, Tran HQ, Bhatti AK, Manon V, Young S, Wong ME: Is Reconstruction of Large Mandibular Defects Using Bioengineering Materials Effective? J Oral Maxillofac Surg, 78(4):661.e1-661.e29, 2020.
Associate professors James C. Melville, DDS; and Simon W. Young, DDS, MD, PhD, from the Bernard and Gloria Pepper Katz Department of Oral and Maxillofacial Surgery at UTHealth Houston School of Dentistry have jointly received the 2023 Clinical Research Award from the American Association of Oral and Maxillofacial Surgeons.
American College of Surgeons Mentoring Webinar
OMS Research – The Future of the Specialty Depends on It
Everyday Oral Surgery: Surgeons Talking Shop: Dr. Simon Young: Pearls On Doing Research as an OMS
Teeth & Titanium Ep: 22: OMFS Research with Dr. Simon Young
Care to Know Live: Peer Perspective with Dr. Simon Young
Excited to share a story highlighting our lab's work in the International Association of OMS October 2021 issue of Face to Face which discusses disruptive technology and innovation in OMS:
https://issuu.com/iaoms/docs/face_to_face_october_2021/1?ff
