Bio

Professional Education


  • IRTA Fellow, National Heart, Lung, Blood Institute (2012)

Research & Scholarship

Lab Affiliations


Publications

All Publications


  • Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: A retrospective case-control study JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Lee, C., Li, S., Duy Cong Tran, Zhu, G., Kim, J., Kwong, B. Y., Chang, A. S. 2018; 79 (6): 1047?52
  • Response to the Letter to the Editor entitled, "Use of immortal time within survival analysis": JAAD-D-18-01157. Journal of the American Academy of Dermatology Min Lee, C. K., Li, S., Tran, D. C., Zhu, G. A., Kim, J., Kwong, B. Y., Chang, A. L. 2018

    View details for PubMedID 30205131

  • An exploratory, open-label, investigator-initiated study to evaluate the efficacy and safety of combination sonidegib and buparlisib for advanced basal cell carcinomas Duy Tran, Zhu, A., Chang, A. MOSBY-ELSEVIER. 2018: AB38
  • Reaction patterns of dermatitis arising during PD-1/PD-L1 inhibitor therapy and association with tumor response Lee, C., Li, S., Zhu, A., Kim, J., Duy Tran, Kwong, B., Chang, A. MOSBY-ELSEVIER. 2018: AB239
  • Differences in skin aging characteristics in women of East Asian versus European descent residing in the same geographic location Guan, L., Zhu, A., Li, S., Montana, M., Kern, D., Knaggs, H., Chang, A. MOSBY-ELSEVIER. 2018: AB108
  • Characterization of dermatitis after PD-1/PD-L1 inhibitor therapy and association with multiple oncologic outcomes: a retrospective case-control study. Journal of the American Academy of Dermatology Min Lee, C. K., Li, S., Tran, D. C., Zhu, G. A., Kim, J., Kwong, B. Y., Chang, A. L. 2018

    Abstract

    BACKGROUND: Cutaneous adverse events are common with Programmed Death (PD)-1/ PD-Ligand (L)1 inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized.OBJECTIVE: (s): To assess the nature of dermatitis after PD-1/PD-L1 inhibitor exposure and oncologic outcomes associated with dermatitis.METHODS: Retrospective, matched, case-control study conducted at a single academic center.RESULTS: The most common histologic patterns were lichenoid dermatitis (50%) and spongiotic dermatitis (40%). Overall tumor response rate was 65.0% for cases and 17.0% for controls (p=0.0007), odds ratio: 7.3 (95% CI 2.3-23.1). Progression Free Survival (PFS) and Overall Survival (OS) times were significantly longer for cases than controls by Kaplan-Meier analysis (p<0.0001 and 0.0203, respectively).LIMITATIONS: Retrospective design and relatively small sample size precluded matching on all cancer types.CONCLUSION: Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The predictive value of PD-1/PD-L1 related dermatitis on cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types.

    View details for PubMedID 29857011

  • An exploratory open- label, investigator-initiated study to evaluate the efficacy and safety of combination sonidegib and buparlisib for advanced basal cell carcinomas JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Tran, D., Moffat, A., Brotherton, R., Pague, A., Zhu, G., Chang, A. S. 2018; 78 (5): 1011?13

    View details for PubMedID 29175429

  • Initial in vitro functional characterization of serum exosomal microRNAs from patients with metastatic basal cell carcinoma Zhu, G., Tran, D. C., Chang, J., Li, R., Spitale, R., Chang, A. S. ELSEVIER SCIENCE INC. 2017: S16
  • An open-label investigator initiated study to evaluate the efficacy and safety of sonidegib and buparlisib in advanced basal cell carcinomas (NCT02303041) Tran, D. C., Zhu, G., Chang, A. S. ELSEVIER SCIENCE INC. 2017: S58
  • Association Between Programmed Death Ligand 1 Expression in Patients With Basal Cell Carcinomas and the Number of Treatment Modalities. JAMA dermatology Chang, J., Zhu, G. A., Cheung, C., Li, S., Kim, J., Chang, A. L. 2017

    Abstract

    Response to programmed death 1 (PD-1) inhibitors has been associated with programmed death ligand 1 (PD-L1) expression levels in several cancers, but PD-L1 expression and its clinical significance in basal cell carcinoma (BCC) are unknown to date.To assess PD-L1 expression in treatment-naive and treated BCCs.This investigation was a cross-sectional study at a single academic tertiary referral center. Immunohistochemical staining on formalin-fixed BCCs from a dermatology clinic were examined in masked fashion by a dermatopathologist and a dermatologist. The study dates were March 31, 2014, to June 7, 2016.Treated BCCs (including those recurrent after surgery, radiotherapy, systemic chemotherapy, or topical chemotherapy) vs treatment-naive BCCs.Percentage of tumor cells and tumor-infiltrating lymphocytes (TILs) with PD-L1 expression, intensities of expression, and association with treatment modalities.Among 138 BCCs from 62 patients (43 males and 19 females; mean [SD] age at biopsy, 61.6 [13.7] years), 89.9% (124 of 138) were positive for PD-L1 expression in tumor cells, and 94.9% (131 of 138) were positive for PD-L1 expression in TILs, defined as greater than 5% positive immunohistochemical staining in the respective cell populations. The PD-L1 immunohistochemical staining intensity of 78 treated BCCs compared with 60 treatment-naive BCCs was significantly different in tumor cells (32% vs 7%, P?=?.003) and TILs (47% vs 18%, P?=?.008) after adjusting for the age at diagnosis. In a multivariable model adjusting for age, sex, and BCC location, PD-L1 staining intensity in tumor cells increased with the number of distinct prior treatment modalities (median, 0.12; interquartile range, 0.03-0.20; P?=?.007).Our data suggest that PD-1 immunotherapy may have activity against BCCs, including in those that have been previously treated. This hypothesis needs to be tested in future clinical trials.

    View details for DOI 10.1001/jamadermatol.2016.5062

    View details for PubMedID 28259105

  • Initial in vitro functional characterization of serum exosomal microRNAs from patients with metastatic basal cell carcinoma British Journal of Dermatology Chang, D. J., et al 2017; March: e187?e190

    View details for DOI 10.1111/bjd.15508

  • Retrospective analysis of inpatient dermatology consultations for cancer patients Guerrero, A. M., Zhu, G. A., Kwong, B. ELSEVIER SCIENCE INC. 2016: S28
  • Identification of metastasis-associated microRNAs in basal cell carcinoma Chang, J., Zhu, G. A., Li, R., Antes, T., Spitale, R., Chang, A. S. MOSBY-ELSEVIER. 2016: AB199
  • PDL1 and CD8 expression in basal cell carcinoma correlates with response to Hedgehog inhibitor therapy Chang, J., Zhu, G. A., Li, S., Kim, J., Chang, A. S. ELSEVIER SCIENCE INC. 2016: S44
  • Identification of metastasis-associated exosomal microRNAs in basal cell carcinoma Chang, J., Zhu, G. A., Li, R., Antes, T., Spitale, R., Chang, A. S. ELSEVIER SCIENCE INC. 2016: S18
  • Discordance in routine second opinion pathology review of head and neck oncology specimens: A single-center five year retrospective review ORAL ONCOLOGY Zhu, G. A., Lira, R., Colevas, A. D. 2016; 53: 36-41

    Abstract

    Second opinion review of pathology specimens is a common institutional practice, supported by large retrospective studies demonstrating significant histologic discordance. Since the most recent study of head and neck-specific pathology review was conducted, routine HPV and EBV testing is now recommended for certain specimens. We describe the frequency of and reasons for discordant reports and their potential impact on treatment recommendations and prognosis in a five-year retrospective cohort study at a single academic referral institution from 2005 to 2010.Following institutional review board review, 1003 cases referred to the Head and Neck Oncology Service were identified using a retrospective database search. Discordance between outside and second review pathology report was assessed by a board-certified medical oncologist.667 cases were included, of which 22% were discordant. Discordance was associated with adenocarcinomas (AOR [adjusted odds ratio] 0.09, 95% CI 0.03-0.31; p<0.001), poorly differentiated carcinomas (AOR 0.14, 95% CI 0.06-0.39; p<0.001), and specimens of uncommon histology (AOR 0.18, 95% CI 0.07-0.45; p<0.001) but not biopsy site in a multivariate model. The most common reasons for discordance included histology (61%), followed by the results of special studies (36%), and the presence or absence of stromal invasion (14%). Differences in tumor HPV status comprised 16% of discordant cases and were associated with better prognosis (p<0.001) following second opinion review.Routine second opinion pathology review may lead to clinically significant differences in treatment recommendations and prognosis.

    View details for DOI 10.1016/j.oraloncology.2015.11.018

    View details for Web of Science ID 000367523100006

  • Estimation of individual cumulative ultraviolet exposure using a geographically-adjusted, openly-accessible tool BioMed Central Dermatology Zhu, G. A., Raber, I., Sakshuwong, S., Li, A., Tan, C., Chang, A. S. 2016: 1

    Abstract

    Estimates of an individual's cumulative ultraviolet (UV) radiation exposure can be useful since ultraviolet radiation exposure increases skin cancer risk, but a comprehensive tool that is practical for use in the clinic does not currently exist. The objective of this study is to develop a geographically-adjusted tool to systematically estimate an individual's self-reported cumulative UV radiation exposure, investigate the association of these estimates with skin cancer diagnosis, and assess test reliability.A 12-item online questionnaire from validated survey items for UV exposure and skin cancer was administered to online volunteers across the United States and results cross-referenced with UV radiation indices. Cumulative UV exposure scores (CUES) were calculated and correlated with personal history of skin cancer in a case-control design. Reliability was assessed in a separate convenience sample.1,118 responses were included in the overall sample; the mean age of respondents was 46 (standard deviation 15, range 18 - 81) and 150 (13 %) reported a history of skin cancer. In bivariate analysis of 1:2 age-matched cases (n?=?149) and controls (n?=?298), skin cancer cases were associated with (1) greater CUES prior to first skin cancer diagnosis than controls without skin cancer history (242,074 vs. 205,379, p?=?0.003) and (2) less engagement in UV protective behaviors (p?

    View details for DOI 10.1186/s12895-016-0038-1

    View details for PubMedCentralID PMC4721109

  • Estimation of individual cumulative ultraviolet exposure using a geographically-adjusted, openly-accessible tool. BMC dermatology Zhu, G. A., Raber, I., Sakshuwong, S., Li, S., Li, A. S., Tan, C., Chang, A. L. 2016; 16 (1): 1-?

    Abstract

    Estimates of an individual's cumulative ultraviolet (UV) radiation exposure can be useful since ultraviolet radiation exposure increases skin cancer risk, but a comprehensive tool that is practical for use in the clinic does not currently exist. The objective of this study is to develop a geographically-adjusted tool to systematically estimate an individual's self-reported cumulative UV radiation exposure, investigate the association of these estimates with skin cancer diagnosis, and assess test reliability.A 12-item online questionnaire from validated survey items for UV exposure and skin cancer was administered to online volunteers across the United States and results cross-referenced with UV radiation indices. Cumulative UV exposure scores (CUES) were calculated and correlated with personal history of skin cancer in a case-control design. Reliability was assessed in a separate convenience sample.1,118 responses were included in the overall sample; the mean age of respondents was 46 (standard deviation 15, range 18 - 81) and 150 (13 %) reported a history of skin cancer. In bivariate analysis of 1:2 age-matched cases (n?=?149) and controls (n?=?298), skin cancer cases were associated with (1) greater CUES prior to first skin cancer diagnosis than controls without skin cancer history (242,074 vs. 205,379, p?=?0.003) and (2) less engagement in UV protective behaviors (p?

    View details for DOI 10.1186/s12895-016-0038-1

    View details for PubMedID 26790927

    View details for PubMedCentralID PMC4721109

  • Overall and progression-free survival of stage 4 cutaneous squamous cell carcinoma at a single large referral center JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY Zhu, G., Chang, A. 2015; 73 (1): 165?66

    View details for PubMedID 26089053

  • Geographically adjusted tool to estimate self-reported cumulative ultraviolet exposure and associated skin cancer risk Raber, I., Zhu, G., Li, S., Sakshuwong, S., Li, A., Tan, C. Z., Chang, A. S. NATURE PUBLISHING GROUP. 2015: S40
  • Serum exosomes from metastatic basal cell carcinoma patients confer increased metabolic activity in cultured primary human fibroblasts Zhu, G., Antes, T., Spitale, R., Chang, A. S. NATURE PUBLISHING GROUP. 2015: S22
  • Acquiring snapshots of the orientation of trans-membrane protein domains using a hybrid FRET pair FEBS LETTERS Gahl, R. F., Tekle, E., Zhu, G. A., Taraska, J. W., Tjandra, N. 2015; 589 (8): 885-889

    Abstract

    One challenge in studying the function of membrane-embedded proteins is determining the orientation of key domains in the context of the changing and dynamic membrane environment. We describe a confocal microscopy setup that utilizes external electric field pulses to direct dipicrylamine (DPA) to a membrane leaflet. The detection of FRET between DPA and a fluorescent probe attributes it to the inner or outer leaflet of a membrane. By utilizing short acquisition times and confocal imaging, this attribution could be made even in changing membrane environments. Our setup adds versatility to the study of the biological activity of membrane-embedded proteins.

    View details for DOI 10.1016/j.febslet.2015.02.030

    View details for Web of Science ID 000351265800003

    View details for PubMedID 25747388

  • Gender differences in HIV risk behaviors in individuals recently released from prison: results of a pilot study Health & Justice Zhu, G. A., Birnbaum, N., Carroll-Scott, A., Evans, L., Fiellin, L. E., Wang, E. A. 2015; 3 (6)
  • Two Different Scenarios of Squamous Cell Carcinoma Within Advanced Basal Cell Carcinomas Cases Illustrating the Importance of Serial Biopsy During Vismodegib Usage JAMA DERMATOLOGY Zhu, G. A., Sundram, U., Chang, A. L. 2014; 150 (9): 970-973

    Abstract

    IMPORTANCE Vismodegib is a Hedgehog signaling pathway inhibitor recently approved by the US Food and Drug Administration for advanced basal cell carcinoma. We present 2 cases of clinically significant squamous cell carcinoma within the tumor bed of locally advanced basal cell carcinoma found during vismodegib treatment. OBSERVATIONS The first case is that of a patient with locally advanced basal cell carcinoma responsive to vismodegib but with an enlarging papule within the tumor bed. On biopsy, this papule was an invasive acantholytic squamous cell carcinoma. The second case is that of a patient with Gorlin syndrome with a locally advanced basal cell carcinoma that was stable while the patient was receiving therapy with vismodegib for 2.5 years but subsequently increased in size. Biopsy specimens from this tumor showed invasive squamous cell carcinoma, spindle cell subtype. In both cases, the squamous cell carcinomas were surgically resected. CONCLUSIONS AND RELEVANCE These cases highlight the importance of repeated biopsy in locally advanced basal cell carcinomas in 2 clinical situations: (1) when an area within the tumor responds differentially to vismodegib, and (2) when a tumor stops being suppressed by vismodegib. Timely diagnosis of non-basal cell histologic characteristics is critical to institution of effective therapy.

    View details for DOI 10.1001/jamadermatol.2014.583

    View details for Web of Science ID 000345273800013

  • Patient With Gorlin Syndrome and Metastatic Basal Cell Carcinoma Refractory to Smoothened Inhibitors JAMA DERMATOLOGY Zhu, G. A., Li, A. S., Chang, A. L. 2014; 150 (8): 877-879

    Abstract

    IMPORTANCE Basal cell carcinomas (BCCs) in patients with Gorlin syndrome have been reported to be extremely sensitive to Smoothened (SMO) inhibitors, a novel targeted therapy against the Hedgehog pathway, because of characteristic mutations in these patients. A few cases of disease refractory to oral therapy with SMO inhibitors have been reported in patients with Gorlin syndrome and nonmetastatic BCCs, but refractory disease in distantly metastatic tumors has not been documented in this high-risk group. OBSERVATIONS A man with Gorlin syndrome and innumerable cutaneous BCCs presented with biopsy-proven BCC in his lungs. After SMO inhibitor therapy, almost all of his cutaneous tumors shrank, but his lung metastases did not. These lung metastases remained refractory to treatment despite institution of a second SMO inhibitor. CONCLUSIONS AND RELEVANCE We report a case of Gorlin syndrome in a patient with metastatic BCC refractory to SMO inhibitors. Furthermore, clinical responses in this patient's cutaneous tumors did not parallel the responses in the distant site. However, serial imaging after diagnosis of metastatic disease can be critical to monitor for response to therapy.

    View details for DOI 10.1001/jamadermatol.2013.8744

    View details for Web of Science ID 000345271000014

  • Overall and progression-free survival in metastatic basosquamous cancer: A case series. Journal of the American Academy of Dermatology Zhu, G. A., Danial, C., Liu, A., Li, S., Su Chang, A. L. 2014; 70 (6): 1145-1146

    View details for DOI 10.1016/j.jaad.2014.03.003

    View details for PubMedID 24831322

  • Review of pathologic diagnosis in head and neck cancer patients: Why do it? Zhu, G., Lira, R. R., Colevas, A. AMER SOC CLINICAL ONCOLOGY. 2014
  • Development of a geographically-adjusted tool to more accurately estimate self-reported cumulative ultraviolet exposure: A two-part study Zhu, G., Li, A., Chang, A. S. NATURE PUBLISHING GROUP. 2014: S54
  • Similarity in survival in stage 4 basosquamous carcinoma and stage 4 squamous cell carcinoma: Results of a single-site retrospective cohort study Zhu, G. A., Danial, C., Liu, A., Li, S., Chang, A. L. NATURE PUBLISHING GROUP. 2014: S90
  • A useable and comprehensive tool to estimate cumulative lifetime ultraviolet exposure Li, A., Chang, A. S., Zhu, G. A. MOSBY-ELSEVIER. 2014: AB153
  • Oral smoothened inhibitor for advanced basal cell carcinoma of the hand: a case report. Hand (New York, N.Y.) Zhu, G. A., Chen, A., Chang, A. L. 2014; 9 (1): 127-128

    View details for DOI 10.1007/s11552-013-9555-0

    View details for PubMedID 24570650

  • Oral Smoothened Inhibitor for Advanced Basal Cell Carcinoma of the Hand: A Case Report HAND Zhu, G. A., Chen, A., Chang, A. S. 2014; 9 (1): 127-8
  • A PILOT STUDY EXAMINING FOOD INSECURITY AND HIV RISK BEHAVIORS AMONG INDIVIDUALS RECENTLY RELEASED FROM PRISON AIDS EDUCATION AND PREVENTION Wang, E. A., Zhu, G. A., Evans, L., Carroll-Scott, A., Desai, R., Fiellin, L. E. 2013; 25 (2): 112-123

    Abstract

    Annually 700,000 individuals are released from U.S. prison, many at risk for food insecurity and HIV. The association between food insecurity and HIV risk behaviors has been established but not in this population. To investigate this association, we recruited 110 recently released prisoners to participate in a survey. Ninety-one percent of our sample was food insecure; 37% did not eat for an entire day in the past month. Those who did not eat for an entire day were more likely to report using alcohol, heroin, or cocaine before sex or exchanging sex for money compared to those who had at least a meal each day. From this pilot study, released prisoners appear to be at risk for food insecurity, and not eating for an entire day is associated with certain HIV risk behaviors. HIV prevention efforts should include longitudinal studies on the relationship between food insecurity and HIV risk behaviors among recently released prisoners.

    View details for Web of Science ID 000316922100003

    View details for PubMedID 23514079

  • Artificial membrane-like environments for in vitro studies of purified G-protein coupled receptors BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES Serebryany, E., Zhu, G. A., Yan, E. C. 2012; 1818 (2): 225-233

    Abstract

    Functional reconstitution of transmembrane proteins remains a significant barrier to their biochemical, biophysical, and structural characterization. Studies of seven-transmembrane G-protein coupled receptors (GPCRs) in vitro are particularly challenging because, ideally, they require access to the receptor on both sides of the membrane as well as within the plane of the membrane. However, understanding the structure and function of these receptors at the molecular level within a native-like environment will have a large impact both on basic knowledge of cell signaling and on pharmacological research. The goal of this article is to review the main classes of membrane mimics that have been, or could be, used for functional reconstitution of GPCRs. These include the use of micelles, bicelles, lipid vesicles, nanodiscs, lipidic cubic phases, and planar lipid membranes. Each of these approaches is evaluated with respect to its fundamental advantages and limitations and its applications in the field of GPCR research. This article is part of a Special Issue entitled: Membrane protein structure and function.

    View details for DOI 10.1016/j.bbamem.2011.07.047

    View details for Web of Science ID 000300380000014

    View details for PubMedID 21851807

  • G Protein?Coupled Receptors Encyclopedia of Supramolecular Chemistry Zhu, G. A., Serebryany, E., Yan, E. C. Taylor & Francis. 2012

    View details for DOI 10.1081/E-ESMC-120048282

  • Chemical Kinetic Analysis of Thermal Decay of Rhodopsin Reveals Unusual Energetics of Thermal Isomerization and Hydrolysis of Schiff Base JOURNAL OF BIOLOGICAL CHEMISTRY Liu, J., Liu, M. Y., Fu, L., Zhu, G. A., Yan, E. C. 2011; 286 (44): 38408-38416

    Abstract

    The thermal properties of rhodopsin, which set the threshold of our vision, have long been investigated, but the chemical kinetics of the thermal decay of rhodopsin has not been revealed in detail. To understand thermal decay quantitatively, we propose a kinetic model consisting of two pathways: 1) thermal isomerization of 11-cis-retinal followed by hydrolysis of Schiff base (SB) and 2) hydrolysis of SB in dark state rhodopsin followed by opsin-catalyzed isomerization of free 11-cis-retinal. We solve the kinetic model mathematically and use it to analyze kinetic data from four experiments that we designed to assay thermal decay, isomerization, hydrolysis of SB using dark state rhodopsin, and hydrolysis of SB using photoactivated rhodopsin. We apply the model to WT rhodopsin and E181Q and S186A mutants at 55 C, as well as WT rhodopsin in H(2)O and D(2)O at 59 C. The results show that the hydrogen-bonding network strongly restrains thermal isomerization but is less important in opsin and activated rhodopsin. Furthermore, the ability to obtain individual rate constants allows comparison of thermal processes under various conditions. Our kinetic model and experiments reveal two unusual energetic properties: the steep temperature dependence of the rates of thermal isomerization and SB hydrolysis in the dark state and a strong deuterium isotope effect on dark state SB hydrolysis. These findings can be applied to study pathogenic rhodopsin mutants and other visual pigments.

    View details for DOI 10.1074/jbc.M111.280602

    View details for Web of Science ID 000296594200055

    View details for PubMedID 21921035

Footer Links:

Stanford Medicine Resources: