Bio

Clinical Focus


  • Cancer > Head and Neck Cancer
  • Parotid Neoplasms
  • Salivary Gland Neoplasms
  • Skull Base Neoplasms
  • Surgical Flaps
  • Sialoendoscopy
  • Jaw
  • Otolaryngology
  • Neck Dissection
  • Carcinoma, Skin Appendage

Academic Appointments


Administrative Appointments


  • Chief of Otolaryngology, VA Palo Alto (2012 - Present)

Honors & Awards


  • Faculty Teaching Award, Stanford Department of Otolaryngology (2013)

Professional Education


  • Fellowship:University of Washington Medical Center (2009) WA
  • Board Certification: Otolaryngology, American Board of Otolaryngology (2010)
  • Residency:Washington University School Of Medicine (2008) MO
  • Internship:Washington University School Of Medicine (2002) MO
  • Medical Education:University of Arizona College of Medicine (2001) AZ

Research & Scholarship

Current Research and Scholarly Interests


Innovation of devices to improve the quality of life of patients with advanced head and neck cancers, Microvascular free flap reconstruction of large head and neck defects to restore cosmesis and function (speech, swallowing), stem cell recovery of radiation induced salivary damage, and salivary gland cancer biology

Clinical Trials


  • NBI to Characterize Patterns of Vascular Supply Within Lymphoepithelial Mucosa in Oropharyngeal Cancer Recruiting

    The purpose of this study is to characterize the blood supply at the base of the tongue and within the tonsil region. We hypothesize that high-resolution Narrow Band Imaging (NBI) will improve the diagnosis of oropharyngeal carcinoma (OPC). The goal is to provide the better assessment of tumor and thus providing better preoperative expectations to patients with OPC or tumor extent prior to radiation therapy.

    View full details

Teaching

2014-15 Courses


Publications

Journal Articles


  • CD271 is a functional and targetable marker of tumor-initiating cells in head and neck squamous cell carcinoma. Oncotarget Murillo-Sauca, O., Chung, M. K., Shin, J. H., Karamboulas, C., Kwok, S., Jung, Y. H., Oakley, R., Tysome, J. R., Farnebo, L. O., Kaplan, M. J., Sirjani, D., Divi, V., Holsinger, F. C., Tomeh, C., Nichols, A., Le, Q. T., Colevas, A. D., Kong, C. S., Uppaluri, R., Lewis, J. S., Ailles, L. E., Sunwoo, J. B. 2014; 5 (16): 6854-6866

    Abstract

    Tumor-initiating cells (TICs) in squamous cell carcinoma of the head and neck (SCCHN) are best characterized by their surface expression of CD44. Although there is great interest in identifying strategies to target this population, no marker of these cells has been found to be functionally active. Here, we examined the expression of the purported marker of normal human oral epithelial stem cells, CD271. We show that CD271 expression is restricted to a subset of the CD44+ cells. Using xenograft assays, we show that the CD44+CD271+ subpopulation contains the most tumorigenic cells. Loss of CD271 function results in a block in the G2-M phase of the cell cycle and a profound negative impact on the capacity of these cells to initiate tumor formation in vivo. Incubation with recombinant NGF results in enhanced phosphorylation of Erk, providing additional evidence that CD271 is functionally active. Finally, incubation of SCCHN cells with antibody to CD271 results in decreased Erk phosphorylation and decreased tumor formation in vivo. Thus, our data are the first to demonstrate that CD271 more specifically identifies the TIC subpopulation within the CD44+ compartment in SCCHN and that this receptor is a functionally active and targetable molecule.

    View details for PubMedID 25149537

  • Neurotrophic factor GDNF promotes survival of salivary stem cells. journal of clinical investigation Xiao, N., Lin, Y., Cao, H., Sirjani, D., Giaccia, A. J., Koong, A. C., Kong, C. S., Diehn, M., Le, Q. 2014; 124 (8): 3364-3377

    Abstract

    Stem cell-based regenerative therapy is a promising treatment for head and neck cancer patients that suffer from chronic dry mouth (xerostomia) due to salivary gland injury from radiation therapy. Current xerostomia therapies only provide temporary symptom relief, while permanent restoration of salivary function is not currently feasible. Here, we identified and characterized a stem cell population from adult murine submandibular glands. Of the different cells isolated from the submandibular gland, this specific population, Lin-CD24+c-Kit+Sca1+, possessed the highest capacity for proliferation, self renewal, and differentiation during serial passage in vitro. Serial transplantations of this stem cell population into the submandibular gland of irradiated mice successfully restored saliva secretion and increased the number of functional acini. Gene-expression analysis revealed that glial cell line-derived neurotrophic factor (Gdnf) is highly expressed in Lin-CD24+c-Kit+Sca1+ stem cells. Furthermore, GDNF expression was upregulated upon radiation therapy in submandibular glands of both mice and humans. Administration of GDNF improved saliva production and enriched the number of functional acini in submandibular glands of irradiated animals and enhanced salisphere formation in cultured salivary stem cells, but did not accelerate growth of head and neck cancer cells. These data indicate that modulation of the GDNF pathway may have potential therapeutic benefit for management of radiation-induced xerostomia.

    View details for DOI 10.1172/JCI74096

    View details for PubMedID 25036711

  • A Novel Aldehyde Dehydrogenase-3 Activator (Alda-89) Protects Submandibular Gland Function from Irradiation without Accelerating Tumor Growth CLINICAL CANCER RESEARCH Xiao, N., Cao, H., Chen, C., Kong, C. S., Ali, R., Chan, C., Sirjani, D., Graves, E., Koong, A., Giaccia, A., Mochly-Rosen, D., Quynh-Thu Le, Q. T. 2013; 19 (16): 4455-4464
  • A novel aldehyde dehydrogenase-3 activator (Alda-89) protects submandibular gland function from irradiation without accelerating tumor growth. Clinical cancer research Xiao, N., Cao, H., Chen, C., Kong, C. S., Ali, R., Chan, C., Sirjani, D., Graves, E., Koong, A., Giaccia, A., Mochly-Rosen, D., Le, Q. 2013; 19 (16): 4455-4464

    Abstract

    To determine the effect of Alda-89 (an ALDH3 activitor) on (1) the function of irradiated (RT) submandibular gland (SMG) in mice, (2) its toxicity profile and (3) its effect on the growth of head and neck cancer (HNC) in vitro and in vivo.Adult mice were infused with Alda-89 or vehicle before, during and after RT. Saliva secretion was monitored weekly. Hematology, metabolic profile and post-mortem evaluation for toxicity were examined at the time of sacrifice. Alda-89 or vehicle was applied to HNC cell lines in vitro, and SCID mice transplanted with HNC in vivo with or without radiation; HNC growth was monitored. The ALDH3A1 and ALDH3A2 protein expression was evaluated in 89 HNC patients and correlated to freedom from relapse (FFR) and overall survival (OS).Alda-89 infusion significantly resulted in more whole saliva production and a higher percentage of preserved acini after RT compared to vehicle control. There was no difference in the complete blood count, metabolic profile, and major organ morphology between the Alda-89 and vehicle groups. Compared to vehicle control, Alda-89 treatment did not accelerate HNC cell proliferation in vitro, nor did it affect tumor growth in vivo with or without RT. Higher expression of ALDH3A1 or ALDH3A2 was not significantly associated with worse FFR or OS in either HPV-positive or HPV-negative group.Alda-89 preserves salivary function after RT without affecting HNC growth or causing measurable toxicity in mice. It is a promising candidate to mitigate RT-related xerostomia.

    View details for DOI 10.1158/1078-0432.CCR-13-0127

    View details for PubMedID 23812668

  • Cost-effectiveness landscape analysis of treatments addressing xerostomia in patients receiving head and neck radiation therapy. Oral surgery, oral medicine, oral pathology and oral radiology Sasportas, L. S., Hosford, D. N., Sodini, M. A., Waters, D. J., Zambricki, E. A., Barral, J. K., Graves, E. E., Brinton, T. J., Yock, P. G., Le, Q., Sirjani, D. 2013; 116 (1): e37-51

    Abstract

    Head and neck (H&N) radiation therapy (RT) can induce irreversible damage to the salivary glands thereby causing long-term xerostomia or dry mouth in 68%-85% of the patients. Not only does xerostomia significantly impair patients' quality-of-life (QOL) but it also has important medical sequelae, incurring high medical and dental costs. In this article, we review various measures to assess xerostomia and evaluate current and emerging solutions to address this condition in H&N cancer patients. These solutions typically seek to accomplish 1 of the 4 objectives: (1) to protect the salivary glands during RT, (2) to stimulate the remaining gland function, (3) to treat the symptoms of xerostomia, or (4) to regenerate the salivary glands. For each treatment, we assess its mechanisms of action, efficacy, safety, clinical utilization, and cost. We conclude that intensity-modulated radiation therapy is both the most widely used prevention approach and the most cost-effective existing solution and we highlight novel and promising techniques on the cost-effectiveness landscape.

    View details for DOI 10.1016/j.oooo.2013.02.017

    View details for PubMedID 23643579

  • Cost-effectiveness landscape analysis of treatments addressing xerostomia in patients receiving head and neck radiation therapy ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY Sasportas, L. S., Hosford, D. N., Sodini, M. A., Waters, D. J., Zambricki, E. A., Barral, J. K., Graves, E. E., Brinton, T. J., Yock, P. G., Le, Q., Sirjani, D. 2013; 116 (1): E37-E51
  • Impact of positron emission tomography/computed tomography surveillance at 12 and 24 months for detecting head and neck cancer recurrence CANCER Ho, A. S., Tsao, G. J., Chen, F. W., Shen, T., Kaplan, M. J., Colevas, A. D., Fischbein, N. J., Quon, A., Quynh-Thu Le, Q. T., Pinto, H. A., Fee, W. E., Sunwoo, J. B., Sirjani, D., Hara, W., Yao, M. 2013; 119 (7): 1349-1356

    Abstract

    In head and neck cancer (HNC), 3-month post-treatment positron emission tomography (PET)/computed tomography (CT) reliably identifies persistent/recurrent disease. However, further PET/CT surveillance has unclear benefit. The impact of post-treatment PET/CT surveillance on outcomes is assessed at 12 and 24 months.A 10-year retrospective analysis of HNC patients was carried out with long-term serial imaging. Imaging at 3 months included either PET/CT or magnetic resonance imaging, with all subsequent imaging comprised of PET/CT. PET/CT scans at 12 and 24 months were evaluated only if preceding interval scans were negative. Of 1114 identified patients, 284 had 3-month scans, 175 had 3- and 12-month scans, and 77 had 3-, 12-, and 24-month scans.PET/CT detection rates in clinically occult patients were 9% (15 of 175) at 12 months, and 4% (3 of 77) at 24 months. No difference in outcomes was identified between PET/CT-detected and clinically detected recurrences, with similar 3-year disease-free survival (41% vs 46%, P = .91) and 3-year overall survival (60% vs 54%, P = .70) rates. Compared with 3-month PET/CT, 12-month PET/CT demonstrated fewer equivocal reads (26% vs 10%, P < .001). Of scans deemed equivocal, 6% (5 of 89) were ultimately found to be positive.HNC patients with negative 3-month imaging appear to derive limited benefit from subsequent PET/CT surveillance. No survival differences were observed between PET/CT-detected and clinically detected recurrences, although larger prospective studies are needed for further investigation.

    View details for DOI 10.1002/cncr.27892

    View details for Web of Science ID 000316811900010

  • A Novel Aldehyde Dehydrogenase-3 Activator Leads to Adult Salivary Stem Cell Enrichment In Vivo CLINICAL CANCER RESEARCH Banh, A., Xiao, N., Cao, H., Chen, C., Kuo, P., Krakow, T., Bavan, B., Khong, B., Yao, M., Ha, C., Kaplan, M. J., Sirjani, D., Jensen, K., Kong, C. S., Mochly-Rosen, D., Koong, A. C., Quynh-Thu Le, Q. T. 2011; 17 (23): 7265-7272

    Abstract

    To assess aldehyde dehydrogenase (ALDH) expression in adult human and murine submandibular gland (SMG) stem cells and to determine the effect of ALDH3 activation in SMG stem cell enrichment.Adult human and murine SMG stem cells were selected by cell surface markers (CD34 for human and c-Kit for mouse) and characterized for various other stem cell surface markers by flow cytometry and ALDH isozymes expression by quantitative reverse transcriptase PCR. Sphere formation and bromodeoxyuridine (BrdUrd) incorporation assays were used on selected cells to confirm their renewal capacity and three-dimensional (3D) collagen matrix culture was applied to observe differentiation. To determine whether ALDH3 activation would increase stem cell yield, adult mice were infused with a novel ALDH3 activator (Alda-89) or with vehicle followed by quantification of c-Kit(+)/CD90(+) SMG stem cells and BrdUrd(+) salispheres.More than 99% of CD34(+) huSMG stem cells stained positive for c-Kit, CD90 and 70% colocalized with CD44, Nestin. Similarly, 73.8% c-Kit(+) mSMG stem cells colocalized with Sca-1, whereas 80.7% with CD90. Functionally, these cells formed BrdUrd(+) salispheres, which differentiated into acinar- and ductal-like structures when cultured in 3D collagen. Both adult human and murine SMG stem cells showed higher expression of ALDH3 than in their non-stem cells and 84% of these cells have measurable ALDH1 activity. Alda-89 infusion in adult mice significantly increased c-Kit(+)/CD90(+) SMG population and BrdUrd(+) sphere formation compared with control.This is the first study to characterize expression of different ALDH isozymes in SMG stem cells. In vivo activation of ALDH3 can increase SMG stem cell yield, thus providing a novel means for SMG stem cell enrichment for future stem cell therapy.

    View details for DOI 10.1158/1078-0432.CCR-11-0179

    View details for Web of Science ID 000298133600009

    View details for PubMedID 21998334

  • Lefort I Osteotomy access to the Anterior Skull Base Operative Techniques in Otolaryngology Sirjani DB, Futran N. 2010; 21 (1): 22-25

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