Anna Blumental-Perry
Anna Blumental-Perry
Assistant Professor
Jacobs School of Medicine & Biomedical Sciences
Specialty/Research Focus
Apoptosis and cell death; Cell growth, differentiation and development; Metabolism; Molecular and Cellular Biology; Molecular Basis of Disease; Protein Folding; Protein Function and Structure; Pulmonary; RNA; Stem Cells
Professional Summary:
The endoplasmic reticulum and the mitochondria are parts of a proteostasis network that undergoes age-related changes. The focus of my research has been to understand the adaptive and non-adaptive age-dependent reprogramming of cellular homeostasis in the lungs of smokers, with a focus on mitochondrial and endoplasmic reticulum age–related stress responses in local progenitor cells.
My laboratory is using exposure to cigarette smoke (CS) and to nicotine as model systems for environmentally induced physiological stressors in exposed cells, animals and humans.
We identified the first known mitochondria-encoded small non-coding RNA, mito-ncR-805, that mediates retrograde communication between the mitochondrial and nuclear genomes. During stress, mito-ncR-805 exits the mitochondria, and enters the nucleus, where it maintains the expression of nuclear-encoded mitochondrial genes, and by doing so preserves mitochondrial bioenergetics, and orchestrates adaptation of mitochondrial function to stressful conditions. Currently, we are working to understand the cell type specificity and the molecular mechanisms of the release of mito-ncR-805 from the mitochondria, the mechanism of its entrance into the nucleus, as well as the mechanism of its nuclear function, and the possibility to develop mito-ncR-805 into therapeutics for diseases that have a mitochondrial malfunction component as a leading factor in their pathogenesis.
We delineated the mechanisms of CS-effects on protein folding and identified a protein disulfide isomerase (PDI) as the first known ER target of cigarette smoke induced oxidation. PDI is one of the most abundant redox-sensitive ER resident proteins, and it plays a central role in disulfide bond formation, and redox homeostasis. CS-induced posttranslational PDI oxidation result in the induction of ER Stress Response (ERSR) in vitro and in vivo. Animals deficient in ERSR are fully protected from CS-associated fibrosis, and partially protected from inflammation and emphysema. Our current research aims to delineate redox signaling function of post-transnationally oxidized PDI, and establish which specific components of ERSR are involved and when they should be modulated by therapeutic approaches.
Our technical approach has been multidisciplinary including protein chemistry, cell and
molecular biology, advanced microscopy, genetic engineering, and animal models of disease.
Education and Training:
- Fellowship, Cell Biology and Physiology, University of Pittsburgh (2008)
- PhD, Yeast Genetics and Molecular Biology, The Hebrew University of Jerusalem (2002)
- MS, Human Genetics, The Hebrew University of Jerusalem, Magna Cum Laude (1995)
- Pre-Med, Rigas Medical School, Magna Cum Laude (1992)
Employment:
- Assistant Professor, University at Buffalo (2020-present)
- Adjunct Assistant Professor, Case Western Reserve University (2015–2019)
- Assistant Professor, Mercer University (2010–2014)
- Research Instructor, Medicine, University of Pittsburgh (2008–2010)
Awards and Honors:
- Science Daily mentioning (2016)
- Dr Shmerler Foundation Award for Msc Thesis with distinction (1995)
- The Golda Meir Foundation Award for Master Students with distinction (1993)
- Rigas Medical School Dean List Scholarship (1990)
Grants and Sponsored Research:
- September 2010–August 2015
Smoke Induced Unfolded Protein Response in COPD
Flight Attendant Medical Research Institute
Role: Principal Investigator
$324,000 - January 2009–December 2010
Cigarette smoke induced Endoplasmic Reticulum stress response in the pathogenesis of COPD
American Thoracic Society
Role: Principal Investigator
$100,000 - July 2003–June 2005
Phosphoinositides as regulators of Coat protein II complex (COPII) mediated export from Endoplasmic Reticulum
American Heart Association
Role: Principal Investigator
$80,000
Journal Articles:
- Theodore L. Mathuram, Yafei Su, Jonathan E. Bard, Noa A. Perry, Chien Wen Chen, Marisa T. Warren, Phillip A. Linden, Yaron Perry, Maria Hatzoglou, Yun Wu, Anna Blumental-Perry. (2024) Mitochondrial ncRNA LDL-805 declines in alveolar epithelial type 2 cells of chronic obstructive pulmonary disease patients. preprint 10.1101/2024.01.14.575591 has posted on bioRxiv (Jan)
- Mathuram TL, Townsend DM, Lynch VJ, Bederman I, Ye ZW, Zhang J, Sigurdson WJ, Prendergast E, Jobava R, Ferruzza JP, D'Angelo MR, Hatzoglou M, Perry Y, Blumental-Perry A. (2022) A Synthetic Small RNA Homologous to the D-Loop Transcript of mtDNA Enhances Mitochondrial Bioenergetics. Frontiers in physiology (Jan), 13: 772313. doi:10.3389/fphys.2022.772313
- Zhang J, Ye ZW, Chen W, Culpepper J, Jiang H, Ball LE, Mehrotra S, Blumental-Perry A, Tew KD, Townsend DM. (2020) Altered redox regulation and S-glutathionylation of BiP contribute to bortezomib resistance in multiple myeloma. Free radical biology & medicine (Nov), 160: 755-767. doi:10.1016/j.freeradbiomed.2020.09.013
- Blumental-Perry A, Jobava R, Bederman I, Degar AJ, Kenche H, Guan BJ, Pandit K, Perry NA, Molyneaux ND, Wu J, Prendergas E, Ye ZW, Zhang J, Nelson CE, Ahangari F, Krokowski D, Guttentag SH, Linden PA, Townsend DM, Miron A, Kang MJ, Kaminski N, Perry Y, Hatzoglou M. (2020) Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics. Communications biology (Oct), 3(1): 626. doi:10.1038/s42003-020-01322-4
- Krokowski D, Guan BJ, Wu J, Zheng Y, Pattabiraman PP, Jobava R, Gao XH, Di XJ, Snider MD, Mu TW, Liu S, Storrie B, Pearlman E, Blumental-Perry A, Hatzoglou M. (2017) GADD34 Function in Protein Trafficking Promotes Adaptation to Hyperosmotic Stress in Human Corneal Cells. Cell Rep (Dec), 21(10): 2895-2910.
- Kenche H, Ye ZW, Vedagiri K, Richards DM, Gao XH, Tew KD, Townsend DM, Blumental-Perry A. (2016) Adverse Outcomes Associated with Cigarette Smoke Radicals Related to Damage to Protein-disulfide Isomerase. J Biol Chem (Feb), 291(9): 4763-4778.
- Vogelgesang A, Scapin C, Barone C, Tam E, Blumental Perry A, Dammann CE, Blumental-Perry A. (2014) Cigarette smoke exposure during pregnancy alters fetomaternal cell trafficking leading to retention of microchimeric cells in the maternal lung. PLoS One (May), 9(5): 88285-88285.
- Kenche H, Baty CJ, Vedagiri K, Shapiro SD, Blumental-Perry A. (2013) Cigarette smoking affects oxidative protein folding in endoplasmic reticulum by modifying protein disulfide isomerase. FASEB J (Mar), 27(3): 965-977.
- Blumental-Perry A. (2012) Unfolded protein response in chronic obstructive pulmonary disease: smoking, aging and disease: a SAD trifecta. Curr Mol Med (Aug), 12(7): 883-898.
- Minematsu N, Blumental-Perry A, Shapiro SD. (2011) Cigarette smoke inhibits engulfment of apoptotic cells by macrophages through inhibition of actin rearrangement. Am J Respir Cell Mol Biol (Apr), 44(4): 474-482.
- Blumental-Perry A, Haney CJ, Weixel KM, Watkins SC, Weisz OA, Aridor M. (2006) Phosphatidylinositol 4-phosphate formation at ER exit sites regulates ER export. Dev Cell (Nov), 11(5): 671-682.
- Weixel KM, Blumental-Perry A, Watkins SC, Aridor M, Weisz OA. (2005) Distinct Golgi populations of phosphatidylinositol 4-phosphate regulated by phosphatidylinositol 4-kinases. J Biol Chem (Mar), 280(11): 10501-10508.
- Pathre P, Shome K, Blumental-Perry A, Bielli A, Haney CJ, Alber S, Watkins SC, Romero G, Aridor M. (2003) Activation of phospholipase D by the small GTPase Sar1p is required to support COPII assembly and ER export. EMBO J (Aug), 22(16): 4059-4069.
- Blumental-Perry A, Li W, Simchen G, Mitchell AP. (2002) Repression and activation domains of RME1p structurally overlap, but differ in genetic requirements. Mol Biol Cell (May), 13(5): 1709-1721.
- Blumental-Perry A, Zenvirth D, Klein S, Onn I, Simchen G. (2000) DNA motif associated with meiotic double-strand break regions in Saccharomyces cerevisiae. EMBO Rep (Sep), 1(3): 232-238.
Books and Book Chapters:
- Zhi-wei Ye, Jie Zhang, Muhammad Aslam, Anna Blumental-Perry, Kenneth D. Tew, Danyelle M. Townsend. (2023) Chapter Four - Protein disulfide isomerase family mediated redox regulation in cancer. In: Protein disulfide isomerase family mediated redox regulation in cancer, Advances in Cancer Research, Invited. Contributed to writing and editing. July, 2023. https://doi.org/10.1016/bs.acr.2023.06.001. ELSEVIER
Professional Memberships:
- American Society of Biochemistry and Molecular Biology (2015–present)
- National Association of Professional Women (2015–present)
- Pitt Alumni (2009–present)
- American Thoracic Society (2008–present)
- The Hebrew University of Jerusalem Alumni (2002–present)
Presentations:
- "Endoplasmic reticulum and mitochondrial stress responses in the Pathogenesis of Chronic Obstructive Pulmonary Disease" University at Buffalo, Department of Microbiology and Immunology, Invited Speaker Seminar, (2023)
- "Proteostasis imbalance in the pathogenesis of Chronic Obstructive Pulmonary Disease" MD-PhD Seminar Invited Speaker (2023)
- "“Dysregulation of Unfolded Protein Response (UPR) Signaling in Chronic Obstructive Pulmonary Disease (COPD) Leads to Small Airway Fibrotic Disease” https://www.vumedi.com/video/ats-2022-dysregulation-of-unfolded-protein-response-upr-signaling-in-chronic-obstructive-pulmonary-d/" VuMedical a video educational platform for physicians, May 2022. (2022)
- "“Development of a small mtDNA-encoded regulatory non-coding RNA region as a potential therapeutic agent to modulate mitochondrial bioenergetics”" International Conference on COPD and Asthma (2022)
- "Mitochondria-nuclear communication during stress and its possible relevance to cancer cell survival, May 2021" University at Buffalo-Cancer Research Consortium Seminar Series-Guest Speaker (2021)
- "Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics during recovery from stress" International ncRNA world society Invited seminar, April 2021 (2021)
- "Cigarette Smoke Exposure Alters Mitochondria Function by Regulating Expression of Mitochondrial miR805/mitosRNA-L-DL_1 in Alveolar type II Cells" ATS; ATS; Pathologic Programming of Airway Epithelium (2015)
- "Unfolded Protein Response as a Driving Force of Tissue Loss During Virally Induced Exacerbations of Chronic Obstructive Pulmonary Disease" From Unfolded Proteins in the ER to Disease; FASEB Summer Research Conference (2013)
- "Cigarette Smoke Exposure Induces Unfolded Protein Response in Cell Culture and in Animal Models" ATS/AAT-1 foundation meeting; ATS (2010)
- "Unfolded Protein Response Induced by Cigarette Smoke, General Mechanisms and Implications to COPD" From Unfolded Proteins in the ER to Disease; FASEB Summer Research Conference: (2010)
- "Retrograde signaling by an MT-DNA-Encoded non-coding RNA preserves mitochondrial bioenergetics," 11th Targeting Mitochondria Congress, Berlin, October 28-30, 2020.
Service Activities:
- GGB research day poster judge; Judge at research days (2023–present)
- interviewer of potential candidates; PPBS (PhD Program in the Biomedical Sciences) (2023)
- interviewer of potential candidates; Computational Cell Biology, Anatomy and Pathology Graduate program (2023–present)
- Art of Research Competition; Steering Committee member (2022–2023)
- ; Basic Science Representative to Faculty Council Steering Committee (2022–2024)
- ; Basic science representative to Jacobs School Executive Committee Meeting (2022–2024)
- Faculty-member of University at Buffalo Faculty Senate and Faculty Senate Executive Committee.; Basic Science Representative to the Faculty Senate (2022–present)
- Reviewer for PMID: 34566699, PMID: 34916953, and PMID: 34110970; Reviewer (2021–2023)
- ; BCH research day poster and oral presentation judge (2021–2023)
- UB faculty Senate, weekly meeting. Participated in discussion, and voting on certain topics.; Member of the Executive Senate Committee (2020–2022)
- Lung and Aging institutes; Deciphering the Molecular Landscape of Lung Aging in Humans;; Panel Member (2018)
- Lung institute; LIRR;; Grant Reviewer (2017)
- Special Issue “ Pulmonary Case Reports” Journal of Pulmonary & Respiratory Medicine, Published by OmicsGroup; Editor (2013–2014)
- FAMRI; FAMRI;; Grant Reviewer (2012)
- Endoplasmic Reticulum stress in Diseases Journal by De Gruyter; Editor (2012–2019)
- Journal of Pulmonary & Respiratory Medicine; Editorial Board Member (2011–present)
- Am J Respir Cell Mol Biol, Molecular Oncology, Scientific Reports Nature Publishing Group, Journal of Obesity & Weight Loss Therapy, Pulmonary Pha; Reviewer (2011–present)
- Reviewer for Am J Respir Cell Mol Biol, Molecular Oncology, Scientific Reports Nature Publishing Group, Journal of Obesity & Weight Loss Therapy, PlosOne, Frontiers, RNA biology, Clinical&Translational Medicine, Redox Biology; Reviewer (2011–present)