Smita Nair

Overview:

I have 22 years of experience in the field of cancer vaccines and immunotherapy and I am an accomplished T cell immunologist. Laboratory website:
https://surgery.duke.edu/immunology-inflammation-immunotherapy-laboratory

Current projects in the Nair Laboratory:
1] Dendritic cell vaccines using tumor-antigen encoding RNA (mRNA, total tumor RNA, amplified tumor mRNA)
2] Local immune receptor modulation using mRNA that encodes for antibodies, receptor-ligands, cytokines, chemokines and toll-like receptors (current target list: CTLA4, GITR, PD1, TIM3, LAG3, OX40 and 41BB)
3] Combination therapies for cancer: cytotoxic therapy (radiation, chemo and oncolytic poliovirus therapy) with dendritic cell-based vaccines and immune checkpoint blockade
4] Adoptive T cell therapy using tumor RNA-transfected dendritic cells to expand tumor-specific T cells ex vivo
5] Adoptive T cell therapy using PSMA CAR (chimeric antigen receptor) RNA-transfected T cells
6] Direct injection of tumor antigen encoding RNA (targeting antigens to dendric cells in vivo using nanoparticles and aptamers)

Positions:

Professor in Surgery

Surgery, Surgical Sciences
School of Medicine

Professor in Pathology

Pathology
School of Medicine

Professor in Neurosurgery

Neurosurgery
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 1993

University of Tennessee, Knoxville

Grants:

Innate Antiviral Signals for Cancer Immunotherapy

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Co-Principal Investigator
Start Date
End Date

Oncolytic Polovirus, Immunotoxin, and Checkpoint Inhibitor Therapy of Gliomas

Administered By
Neurosurgery, Neuro-Oncology Clinical Research
Awarded By
National Institutes of Health
Role
Co Investigator
Start Date
End Date

Cancer Immunotherapy Through Intratumoral Activation of Recall Responses

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Co-Sponsor
Start Date
End Date

Melanoma-mediated Dendritic Cell Tolerization and Immune Evasion

Administered By
Medicine, Medical Oncology
Awarded By
National Institutes of Health
Role
Co-Mentor
Start Date
End Date

Metabolic Reprogramming of Dendritic Cell-based Cancer Vaccines to Enhance Anti-Tumor Immunity

Administered By
Medicine, Medical Oncology
Awarded By
Alliance for Cancer Gene Therapy
Role
Mentor
Start Date
End Date

Publications:

Abstract P102: Elevated Von Willebrand Factor in Patients Presenting With Large-Vessel Occlusion Stroke as First Symptom of COVID-19 Mirrors Levels in Patients With COVID-19 Requiring ICU-Level Care

<jats:p> <jats:bold>Introduction:</jats:bold> COVID-19 is a coagulopathic disease marked by elevated d-dimers, fibrinogen, and von Willebrand factor (vWF) levels accompanying arterial and venous thrombosis. While the majority of thrombotic events associated with COVID-19 occur in hospitalized patients, a subset of patients with minimal risk factors for CVA but with positive SARS-CoV-2 testing present with stroke as presumed first manifestation of infection. It is unclear if the pro-coagulant milieu present in patients requiring hospitalization for the respiratory complications of COVID-19 is the same as that of patients who present with stroke as first symptom of disease. </jats:p> <jats:p> <jats:bold>Methods:</jats:bold> Following emergent revascularization, clinical vWF levels were measured in patients presenting with stroke who tested positive for COVID-19. In parallel, plasma vWF levels from 28 patients with COVID-19 requiring ICU-level care and 8 healthy volunteers were measured via ELISA. </jats:p> <jats:p> <jats:bold>Results:</jats:bold> Three otherwise healthy patients between the ages of 45-55 years with positive test for SARS-CoV-2 presented with large-vessel stroke. By comparison, the average age of non-COVID stroke patients was 66 years. The consistency of the clots extracted through the aspirating catheter was dark, gelatinous throughout, without evidence of calcification, and distal thrombosis was noted minutes after revascularization. The vWF level for one patient was 345%, while the other two patients had vWF levels &gt;400% of normal, exceeding the upper limit of detection of clinical assays. In the ICU cohort, 12 of 28 had thrombotic events during hospitalization. vWF levels were elevated by a mean of 800% over healthy controls with a range of 230-1670%. </jats:p> <jats:p> <jats:bold>Conclusions:</jats:bold> vWF levels were markedly elevated in both ICU patients and stroke patients with COVID-19 with an overlapping range of elevation over healthy controls. This suggests that widespread endothelial inflammation accompanies infection with SARS-CoV-2 even in the absence of respiratory symptoms. </jats:p>
Authors
Olson, LB; Naqvi, IA; CHEN, L; Que, LG; KRAFT, BD; Nair, SK; Nimjee, SM; Sullenger, BA
MLA Citation
Olson, Lyra B., et al. “Abstract P102: Elevated Von Willebrand Factor in Patients Presenting With Large-Vessel Occlusion Stroke as First Symptom of COVID-19 Mirrors Levels in Patients With COVID-19 Requiring ICU-Level Care.” Stroke, vol. 52, no. Suppl_1, Ovid Technologies (Wolters Kluwer Health), 2021. Crossref, doi:10.1161/str.52.suppl_1.p102.
URI
https://scholars.duke.edu/individual/pub1494672
Source
crossref
Published In
Stroke
Volume
52
Published Date
DOI
10.1161/str.52.suppl_1.p102

Multiplexed, quantitative serological profiling of COVID-19 from a drop of blood by a point-of-care test.

Highly sensitive, specific, and point-of-care (POC) serological assays are an essential tool to manage the COVID-19 pandemic. Here, we report on a microfluidic, multiplexed POC test that can profile the antibody response against multiple SARS-CoV-2 antigens - Spike S1 (S1), Nucleocapsid (N), and the receptor binding domain (RBD) - simultaneously from a 60 microliter drop of blood, plasma, or serum. We assessed the levels of anti-SARS-CoV-2 antibodies in plasma samples from 19 individuals (at multiple time points) with COVID-19 that required admission to the intensive care unit and from 10 healthy individuals. This POC assay shows good concordance with a live virus microneutralization assay, achieved high sensitivity (100%) and specificity (100%), and successfully tracked the longitudinal evolution of the antibody response in infected individuals. We also demonstrated that we can detect a chemokine, IP-10, on the same chip, which may provide prognostic insight into patient outcomes. Because our test requires minimal user intervention and is read by a handheld detector, it can be globally deployed in the fight against COVID-19 by democratizing access to laboratory quality tests.
Authors
Heggestad, JT; Kinnamon, DS; Olson, LB; Liu, J; Kelly, G; Wall, SA; Fontes, CM; Joh, DY; Hucknall, AM; Pieper, C; Naqvi, IA; Chen, L; Que, LG; Oguin, T; Nair, SK; Sullenger, BA; Woods, CW; Sempowski, GD; Kraft, BD; Chilkoti, A
MLA Citation
Heggestad, Jacob T., et al. “Multiplexed, quantitative serological profiling of COVID-19 from a drop of blood by a point-of-care test.Medrxiv, Nov. 2020. Pubmed, doi:10.1101/2020.11.05.20226654.
URI
https://scholars.duke.edu/individual/pub1487524
PMID
33173900
Source
pubmed
Published In
Medrxiv
Published Date
DOI
10.1101/2020.11.05.20226654

Clinical Profile of Neonates with Hypernatremic Dehydration in an Outborn Neonatal Intensive Care Unit.

This hospital-record review describes the clinical profile of hypernatremic dehydration in neonates. 49 neonates (3.4% of the total admitted newborns) developed hypernatremic dehydration between January 2014 and August 2015. The major presenting complaints were fever (34.6%), poor feeding (42.8%), loose stools (40.8%) and lethargy (26.5%). The mean (SD) time needed for correction of hypernatremia was 38.6 (15.1) hours. Exclusively breastfed neonates had lesser complication rates of hypernatremic dehydration.
Authors
Nair, S; Singh, A; Jajoo, M
MLA Citation
Nair, Smita, et al. “Clinical Profile of Neonates with Hypernatremic Dehydration in an Outborn Neonatal Intensive Care Unit.Indian Pediatr, vol. 55, no. 4, Apr. 2018, pp. 301–05.
URI
https://scholars.duke.edu/individual/pub1488969
PMID
29428916
Source
pubmed
Published In
Indian Pediatr
Volume
55
Published Date
Start Page
301
End Page
305

Research Letters

Authors
Nair, S; Singh, A; Jajoo, M; Yadav, P; Sharma, P; Arora, R
MLA Citation
Nair, S., et al. “Research Letters.” Indian Pediatrics, vol. 55, no. 4, Apr. 2018, pp. 343–45. Scopus, doi:10.1007/s13312-018-1268-6.
URI
https://scholars.duke.edu/individual/pub1488970
Source
scopus
Published In
Indian Pediatrics
Volume
55
Published Date
Start Page
343
End Page
345
DOI
10.1007/s13312-018-1268-6

Breast cancer-derived DAMPs enhance cell invasion and metastasis, while nucleic acid scavengers mitigate these effects.

Breast cancer (BC) is the most common malignancy in women. Particular subtypes with aggressive behavior are major contributors to poor outcomes. Triple-negative breast cancer (TNBC) is difficult to treat, pro-inflammatory, and highly metastatic. We demonstrate that TNBC cells express TLR9 and are responsive to TLR9 ligands, and treatment of TNBC cells with chemotherapy increases the release of nucleic-acid-containing damage-associated molecular patterns (NA DAMPs) in cell culture. Such culture-derived and breast cancer patient-derived NA DAMPs increase TLR9 activation and TNBC cell invasion in vitro. Notably, treatment with the polyamidoamine dendrimer generation 3.0 (PAMAM-G3) behaved as a nucleic acid scavenger (NAS) and significantly mitigates such effects. In mice that develop spontaneous BC induced by polyoma middle T oncoprotein (MMTV-PyMT), treatment with PAMAM-G3 significantly reduces lung metastasis. Thus, NAS treatment mitigates cancer-induced inflammation and metastasis and represents a novel therapeutic approach for combating breast cancer.
Authors
Eteshola, EOU; Landa, K; Rempel, RE; Naqvi, IA; Hwang, ES; Nair, SK; Sullenger, BA
MLA Citation
Eteshola, Elias O. U., et al. “Breast cancer-derived DAMPs enhance cell invasion and metastasis, while nucleic acid scavengers mitigate these effects.Mol Ther Nucleic Acids, vol. 26, Dec. 2021, pp. 1–10. Pubmed, doi:10.1016/j.omtn.2021.06.016.
URI
https://scholars.duke.edu/individual/pub1496637
PMID
34513289
Source
pubmed
Published In
Molecular Therapy. Nucleic Acids
Volume
26
Published Date
Start Page
1
End Page
10
DOI
10.1016/j.omtn.2021.06.016