David A. Alagpulinsa, PhD
Research & Publications
Biography
News
Research Summary
Our research program is still burgeoning and primarily focuses on metabolic diseases, with particular emphasis on type 1 diabetes (T1D) and atherosclerotic cardiovascular disease (ASCVD). The etiopathogenesis of T1D is characterized by a detrimental cross-talk between the hematopoietic system and insulin-producing beta cells. There is also evidence that T1D is intrinsically linked with ASCVD above and beyond traditional cardiovascular risk factors. In that vein, our research ideology is that T1D is a cluster of metabolic abnormalities that involves not only the immune system and beta cells, but also the cardiovascular system, and we think that a definitive prevention or cure for T1D may require elimination of both insulin dependence and cardiovascular disease risk, at least, in some patients. We employ a combination of human statistical genetics and genomics, cellular and molecular/biochemical assays, and animal models to understand the pathological mechanisms in the hematopoietic system, beta cells, and the cardiovascular system, and how these are connected in T1D. Our exit plan is to identify and validate disease biomarkers for prediction, precision medicine, and preclinical translation that would facilitate transition to the bedside.
Research Interests
Autoimmune Diseases; Cardiovascular Diseases; Diabetes Mellitus, Type 1; DNA Transposable Elements; Genetics; Hematopoiesis; Hematopoietic Stem Cells; Islets of Langerhans; Myocardial Infarction; Genomics; Atherosclerosis; Epigenomics; Single-Cell Analysis; Clonal Hematopoiesis
Selected Publications
- Short-term function and immune-protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non-human primates without systemic immune suppression: A pilot study.Sremac M, Luo H, Deng H, Parr MFE, Hutcheson J, Verde PS, Alagpulinsa DA, Kitzmann JM, Papas KK, Brauns T, Markmann JF, Lei J, Poznansky MC. Short-term function and immune-protection of microencapsulated adult porcine islets with alginate incorporating CXCL12 in healthy and diabetic non-human primates without systemic immune suppression: A pilot study. Xenotransplantation 2023, e12826. PMID: 37712342, DOI: 10.1111/xen.12826.
- Plasma osteopontin relates to myocardial fibrosis and steatosis and to immune activation among women with HIV.Robinson JA, Toribio M, Quinaglia T, Awadalla M, Talathi R, Durbin CG, Alhallak I, Alagpulinsa DA, Fourman LT, Suero-Abreu GA, Nelson MD, Stanley TL, Longenecker CT, Szczepaniak LS, Jerosch-Herold M, Neilan TG, Zanni MV, Burdo TH. Plasma osteopontin relates to myocardial fibrosis and steatosis and to immune activation among women with HIV. AIDS 2023, 37: 305-310. PMID: 36541642, DOI: 10.1097/QAD.0000000000003417.
- Cardiac strain is lower among women with HIV in relation to monocyte activation.Toribio M, Awadalla M, Drobni ZD, Quinaglia T, Wang M, Durbin CG, Alagpulinsa DA, Fourman LT, Suero-Abreu GA, Nelson MD, Stanley TL, Longenecker CT, Burdo TH, Neilan TG, Zanni MV. Cardiac strain is lower among women with HIV in relation to monocyte activation. PLoS One 2022, 17: e0279913. PMID: 36584183, DOI: 10.1371/journal.pone.0279913.
- Advances in understanding the molecular basis of clonal hematopoiesis.Alagpulinsa DA, Toribio MP, Alhallak I, Shmookler Reis RJ. Advances in understanding the molecular basis of clonal hematopoiesis. Trends Mol Med 2022, 28: 360-377. PMID: 35341686, DOI: 10.1016/j.molmed.2022.03.002.
- Metabolomic and transcriptomic analyses of the anti-rheumatoid arthritis potential of xylopic acid in a bioinspired lipoprotein nanoformulation.Alolga RN, Opoku-Damoah Y, Alagpulinsa DA, Huang FQ, Ma G, Chavez Leon MASC, Kudzai C, Yin X, Ding Y. Metabolomic and transcriptomic analyses of the anti-rheumatoid arthritis potential of xylopic acid in a bioinspired lipoprotein nanoformulation. Biomaterials 2021, 268: 120482. PMID: 33307367, DOI: 10.1016/j.biomaterials.2020.120482.
- Genomic Instability in Multiple Myeloma.Alagpulinsa DA, Szalat RE, Poznansky MC, Shmookler Reis RJ. Genomic Instability in Multiple Myeloma. Trends Cancer 2020, 6: 858-873. PMID: 32487486, DOI: 10.1016/j.trecan.2020.05.006.
- Amplification and overexpression of E2 ubiquitin conjugase UBE2T promotes homologous recombination in multiple myeloma.Alagpulinsa D, Kumar S, Talluri S, Nanjappa P, Buon L, Chakraborty C, Samur M, Szalat R, Shammas M, Munshi N. Amplification and overexpression of E2 ubiquitin conjugase UBE2T promotes homologous recombination in multiple myeloma. Blood Advances 2019, 3: 3968-3972. PMID: 31805191, PMCID: PMC6963244, DOI: 10.1182/bloodadvances.2019000181.
- Alginate-microencapsulation of human stem cell-derived β cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression.Alagpulinsa DA, Cao JJL, Driscoll RK, Sîrbulescu RF, Penson MFE, Sremac M, Engquist EN, Brauns TA, Markmann JF, Melton DA, Poznansky MC. Alginate-microencapsulation of human stem cell-derived β cells with CXCL12 prolongs their survival and function in immunocompetent mice without systemic immunosuppression. Am J Transplant 2019, 19: 1930-1940. PMID: 30748094, DOI: 10.1111/ajt.15308.
- Harnessing CXCL12 signaling to protect and preserve functional β-cell mass and for cell replacement in type 1 diabetes.Alagpulinsa DA, Cao JJL, Sobell D, Poznansky MC. Harnessing CXCL12 signaling to protect and preserve functional β-cell mass and for cell replacement in type 1 diabetes. Pharmacol Ther 2019, 193: 63-74. PMID: 30149101, DOI: 10.1016/j.pharmthera.2018.08.011.
- A Cyclin-Dependent Kinase Inhibitor, Dinaciclib, Impairs Homologous Recombination and Sensitizes Multiple Myeloma Cells to PARP Inhibition.Alagpulinsa DA, Ayyadevara S, Yaccoby S, Shmookler Reis RJ. A Cyclin-Dependent Kinase Inhibitor, Dinaciclib, Impairs Homologous Recombination and Sensitizes Multiple Myeloma Cells to PARP Inhibition. Mol Cancer Ther 2016, 15: 241-50. PMID: 26719576, DOI: 10.1158/1535-7163.MCT-15-0660.
- A peptide nucleic acid targeting nuclear RAD51 sensitizes multiple myeloma cells to melphalan treatment.Alagpulinsa DA, Yaccoby S, Ayyadevara S, Shmookler Reis RJ. A peptide nucleic acid targeting nuclear RAD51 sensitizes multiple myeloma cells to melphalan treatment. Cancer Biol Ther 2015, 16: 976-86. PMID: 25996477, DOI: 10.1080/15384047.2015.1040951.
- A Small-Molecule Inhibitor of RAD51 Reduces Homologous Recombination and Sensitizes Multiple Myeloma Cells to Doxorubicin.Alagpulinsa DA, Ayyadevara S, Shmookler Reis RJ. A Small-Molecule Inhibitor of RAD51 Reduces Homologous Recombination and Sensitizes Multiple Myeloma Cells to Doxorubicin. Front Oncol 2014, 4: 289. PMID: 25401086, DOI: 10.3389/fonc.2014.00289.