Giselle Lopez

Overview:

I am a physician scientist with a clinical focus on neuropathology, and a research interest in brain tumors. Originally from Maryland, I completed my undergraduate training at the University of Maryland, completing degrees in Physiology and Neurobiology as well as Spanish Language and Literature. I subsequently came to Duke for my MD and PhD, and discovered a passion for brain tumor research, and quickly realized that this was my life's calling. After completing a residency and fellowship at the University of California, San Francisco, I returned to Duke as an Assistant Professor of Pathology. Clinically, I now specialize in neuropathology, with my research focusing on brain tumors of all types. By better understanding these tumors, I hope to identify new ways to treat these tumors and improve the lives of patients with brain tumors.

Positions:

Assistant Professor in Pathology

Pathology
School of Medicine

Assistant Professor in Neurosurgery

Neurosurgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

B.S. 2005

University of Maryland, College Park

B.A. 2005

University of Maryland, College Park

MD./PhD. 2014

Duke University School of Medicine

Certificate, Cell And Molecular Biology

Duke University

Residency, Anatomic Pathology

University of California - San Francisco

Fellowship, Neuropathology

University of California - San Francisco

Publications:

Management of glioblastoma: State of the art and future directions.

Glioblastoma is the most common malignant primary brain tumor. Overall, the prognosis for patients with this disease is poor, with a median survival of <2 years. There is a slight predominance in males, and incidence increases with age. The standard approach to therapy in the newly diagnosed setting includes surgery followed by concurrent radiotherapy with temozolomide and further adjuvant temozolomide. Tumor-treating fields, delivering low-intensity alternating electric fields, can also be given concurrently with adjuvant temozolomide. At recurrence, there is no standard of care; however, surgery, radiotherapy, and systemic therapy with chemotherapy or bevacizumab are all potential options, depending on the patient's circumstances. Supportive and palliative care remain important considerations throughout the disease course in the multimodality approach to management. The recently revised classification of glioblastoma based on molecular profiling, notably isocitrate dehydrogenase (IDH) mutation status, is a result of enhanced understanding of the underlying pathogenesis of disease. There is a clear need for better therapeutic options, and there have been substantial efforts exploring immunotherapy and precision oncology approaches. In contrast to other solid tumors, however, biological factors, such as the blood-brain barrier and the unique tumor and immune microenvironment, represent significant challenges in the development of novel therapies. Innovative clinical trial designs with biomarker-enrichment strategies are needed to ultimately improve the outcome of patients with glioblastoma.
Authors
Tan, AC; Ashley, DM; López, GY; Malinzak, M; Friedman, HS; Khasraw, M
MLA Citation
Tan, Aaron C., et al. “Management of glioblastoma: State of the art and future directions.Ca Cancer J Clin, vol. 70, no. 4, July 2020, pp. 299–312. Pubmed, doi:10.3322/caac.21613.
URI
https://scholars.duke.edu/individual/pub1446606
PMID
32478924
Source
pubmed
Published In
Ca: a Cancer Journal for Clinicians
Volume
70
Published Date
Start Page
299
End Page
312
DOI
10.3322/caac.21613

EGFR PHOSPHORYLATION OF DCBLD2 RECRUITS TRAF6 AND STIMULATES AKT-PROMOTED TUMORIGENESIS

Authors
Cheng, S; Feng, H; Lopez, GY; Kim, CK; Duncan, CG; Alvarez, A; Nishikawa, R; Nagane, M; Su, A-J; Auron, PE; Hedberg, ML; Wang, L; Grandis, JR; McLendon, RE; Bigner, DD; Nakano, I; Joshi, K; Kim, S; Lin, H-K; Furnari, FB; Cavenee, WK; Hu, B; Yan, H; Cheng, S-Y
MLA Citation
Cheng, S., et al. “EGFR PHOSPHORYLATION OF DCBLD2 RECRUITS TRAF6 AND STIMULATES AKT-PROMOTED TUMORIGENESIS.” Neuro Oncology, vol. 16, no. suppl 3, Oxford University Press (OUP), 2014, pp. iii16–17. Crossref, doi:10.1093/neuonc/nou206.60.
URI
https://scholars.duke.edu/individual/pub1451307
Source
crossref
Published In
Neuro Oncology
Volume
16
Published Date
Start Page
iii16
End Page
iii17
DOI
10.1093/neuonc/nou206.60

Catastrophic stroke burden in a patient with uncontrolled psoriasis and psoriatic arthritis: a case report.

BACKGROUND: Psoriasis is the most common chronic inflammatory condition involving the T helper cell system. Population studies have demonstrated that patients with psoriasis and/or psoriatic arthritis have an increased risk of developing vascular risk factors, including diabetes, hypertension, and obesity, and increased risk of adverse vascular events, including myocardial infarction and stroke. Population studies have generally investigated the individual contributions of psoriasis and psoriatic arthritis to development of vascular risk factors; fewer studies have investigated the additive contribution of comorbid inflammatory disorders. We present a case of a woman with psoriasis, psoriatic arthritis, and comorbid vascular risk factors. CASE PRESENTATION: A 49 year-old Caucasian woman with a history of severe psoriasis and psoriatic arthritis since adolescence presented with bilateral lower extremity weakness. She was found to have acute bilateral watershed infarcts and multifocal subacute infarcts. Her evaluation revealed vascular risk factors and elevated non-specific systemic inflammatory markers; serum and cerebral spinal fluid did not reveal underlying infection, hypercoagulable state, or vasculitis. Over the course of days, she exhibited precipitous clinical deterioration related to multiple large vessel occlusions, including the bilateral anterior cerebral arteries and the left middle cerebral artery. Autopsy revealed acute thrombi and diffuse, severe atherosclerosis. CONCLUSION: Patients with early onset inflammatory disease activity or comorbid inflammatory disorders may have an even higher risk of developing metabolic syndrome and adverse vascular events compared to patients with late-onset disease activity or with a single inflammatory condition. The described case illustrates the complex relationship between inflammatory disorders and vascular risk factors. The degree of systemic inflammation, as measured by severity of disease activity, has been shown to have a dose-response relationship with comorbid vascular risk factors and vascular events. Dysregulation of the Th1 and Th17 system has been implicated in the development of atherosclerosis and may explain the severe atherosclerosis seen in such chronic inflammatory conditions. Further research will help refine screening and management guidelines to account for comorbid inflammatory disorders and related disease severity.
Authors
Fan, JM; Solomon, DA; López, GY; Hofmann, JW; Colorado, RA; Kim, AS; Meisel, K; Halabi, C
MLA Citation
Fan, Joline M., et al. “Catastrophic stroke burden in a patient with uncontrolled psoriasis and psoriatic arthritis: a case report.Bmc Neurol, vol. 20, no. 1, Mar. 2020, p. 106. Pubmed, doi:10.1186/s12883-020-01681-9.
URI
https://scholars.duke.edu/individual/pub1435907
PMID
32199449
Source
pubmed
Published In
Bmc Neurology
Volume
20
Published Date
Start Page
106
DOI
10.1186/s12883-020-01681-9

POT1 mutation spectrum in tumour types commonly diagnosed among POT1-associated hereditary cancer syndrome families.

BACKGROUND: The shelterin complex is composed of six proteins that protect and regulate telomere length, including protection of telomeres 1 (POT1). Germline POT1 mutations are associated with an autosomal dominant familial cancer syndrome presenting with diverse malignancies, including glioma, angiosarcoma, colorectal cancer and melanoma. Although somatic POT1 mutations promote telomere elongation and genome instability in chronic lymphocytic leukaemia, the contribution of POT1 mutations to development of other sporadic cancers is largely unexplored. METHODS: We performed logistic regression, adjusted for tumour mutational burden, to identify associations between POT1 mutation frequency and tumour type in 62 368 tumours undergoing next-generation sequencing. RESULTS: A total of 1834 tumours harboured a non-benign mutation of POT1 (2.94%), of which 128 harboured a mutation previously reported to confer familial cancer risk in the setting of germline POT1 deficiency. Angiosarcoma was 11 times more likely than other tumours to harbour a POT1 mutation (p=1.4×10-20), and 65% of POT1-mutated angiosarcoma had >1 mutations in POT1. Malignant gliomas were 1.7 times less likely to harbour a POT1 mutation (p=1.2×10-3) than other tumour types. Colorectal cancer was 1.2 times less likely to harbour a POT1 mutation (p=0.012), while melanoma showed no differences in POT1 mutation frequency versus other tumours (p=0.67). CONCLUSIONS: These results confirm a role for shelterin dysfunction in angiosarcoma development but suggest that gliomas arising in the context of germline POT1 deficiency activate a telomere-lengthening mechanism that is uncommon in gliomagenesis.
Authors
Shen, E; Xiu, J; Lopez, GY; Bentley, R; Jalali, A; Heimberger, AB; Bainbridge, MN; Bondy, ML; Walsh, KM
MLA Citation
Shen, Erica, et al. “POT1 mutation spectrum in tumour types commonly diagnosed among POT1-associated hereditary cancer syndrome families.J Med Genet, Jan. 2020. Pubmed, doi:10.1136/jmedgenet-2019-106657.
URI
https://scholars.duke.edu/individual/pub1428973
PMID
31937561
Source
pubmed
Published In
Journal of Medical Genetics
Published Date
DOI
10.1136/jmedgenet-2019-106657

Frequent Mutations of POT1 Distinguish Pulmonary Sarcomatoid Carcinoma From Other Lung Cancer Histologies

© 2020 Elsevier Inc. Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non–small-cell lung cancer (NSCLC) harboring mutations in many canonical NSCLC-driver genes (eg, TP53, KRAS, MET). Protection of telomeres 1 (POT1) mutations are observed in angiosarcoma and chronic lymphocytic leukemia, but their frequency in other solid tumors, including NSCLC subtypes, has not been rigorously explored. Materials and Methods: We analyzed next-generation sequencing data from 62,368 tumors, including 11,134 NSCLCs and 100 PSCs. We performed logistic regression to identify associations between POT1 mutation frequency and tumor histology across 184 tumor categories, adjusting for tumor mutational burden. We further explored co-occurring gene mutations in genes previously reported to underlie PSC tumorigenesis. Results: Across 184 tumor categories, POT1 mutations were most frequent in PSC and were 14 times more common in PSC (28%) than in other tumor types (P = 1.23 × 10-31) and 6.7 times more common in PSC than other NSCLCs (P = 5.1 × 10-17). PSCs harboring KRAS mutations were significantly more likely to harbor POT1 mutations (P = 1.3 × 10-3), whereas those with TP53 mutations were less likely to harbor POT1 mutations (P = .037). One-fourth of POT1-mutated PSCs harbored a second POT1 mutation. Across all PSCs, 83% of POT1 mutations were in the OB1/OB2 (DNA-binding) domain (P = 1.5 × 10-5), an enrichment not observed in other tumor types. Conclusion: We report an unanticipated association between POT1 mutation and PSC. Unlike other molecular alterations that are frequent across NSCLC subtypes, POT1 mutations are largely unique to PSC. This finding may help to develop disease-defining molecular subgroups within PSC and presents opportunities for molecularly stratified prognostication and therapy.
Authors
MLA Citation
Shen, E., et al. “Frequent Mutations of POT1 Distinguish Pulmonary Sarcomatoid Carcinoma From Other Lung Cancer Histologies.” Clinical Lung Cancer, Jan. 2020. Scopus, doi:10.1016/j.cllc.2020.04.002.
URI
https://scholars.duke.edu/individual/pub1441311
Source
scopus
Published In
Clinical Lung Cancer
Published Date
DOI
10.1016/j.cllc.2020.04.002

Research Areas:

Astrocytomas
Cancer
Intracranial tumors
Intracranial tumors in children
Supratentorial brain tumors
Supratentorial brain tumors in children
Tumor Cells, Cultured
Tumor Markers, Biological
Tumor Microenvironment
Tumors
Tumors--Growth