Ashim Malhotra, BPharm, PhD

Phone Number: 
503-352-7295
UC Box: 
A192

Teaching

School of Pharmacy

PHRM 561 | Biochemistry-II

PHRM 568 | Pulmonary, Cardiac and Renal Pathophysiology: Pharmaceutical and Medical Immunology, Inflammation, Cardiovascular and Renal Pathophysiology

PHRM 569 | Pulmonary, Cardiac and Renal Pharmacology

PHRM 581 | Pharmaceutical Sciences: Endocrine and Sex Hormones (Block Coordinator): Biochemistry of diabetes, Metabolic Syndrome

PHRM 583 | Pharmaceutical Sciences: Immunology and Toxicology: Basics of transplant rejection, immunosuppressive pharmacology and therapy

PHRM 766 | Clinical and Serological Immunology (Elective)

School of Audiology

AUD 513 | Pharmacology and Mechanisms of Ototoxicity

Education

2011 | Research Scientist, NYU School of Medicine in New York, New York

2006-2010 | Postdoctoral Fellowship, NYU School of Medicine in New York, New York

2008 | FPGEE Certification, National Association of the Boards of Pharmacy USA

2006 | Doctor of Philosophy, Life Sciences: Biochemistry and Molecular Pharmacology, Saint John’s University in Queens, New York

2003 | Master of Science, Saint John’s University in Queens, New York

2000 | Bachelor of Pharmacy, Hamdard University School of Pharmacy in New Delhi, India

Areas of Research & Specialization

I have two main areas of interest: (1) a pediatric cardiomyopathy called Barth Syndrome and (2) pancreatic cancer. In summary, I employ lipidomics and molecular pharmacology for an elucidation of disease mechanisms.

Barth Syndrome: In cardiomyopathy research, I investigate the molecular pathology of Barth Syndrome (BTHS). BTHS is a rare but fatal, X-linked dilated cardiomyopathy and skeletal myopathy arising due to mutations in the tafazzin gene, the protein product of which is a mitochondrial enzyme of the same name. My work has demonstrated that tafazzin is a transacylase responsible for remodeling the mitochondrial inner membrane phospholipid cardiolipin (CL). We also showed that mutated tafazzin caused myopathic mitochondrial aberrations. Specifically mutated tafazzin containing mitochondria had alterations in lipid profile and evinced cristae membrane collapse involving degenerate supramolecular protein assembly. There were also discrepancies in protein distribution of complex V (ATP synthase) and tafazzin in the mitochondrial supramolecular complexes and therefore perhaps delinquent cristae membrane packing. That this was relevant in the context of cardiocytes was demonstrated when we showed that tafazzin mutations affected mitochondrial development during cardiocyte differentiation. Further, in lymphoblasts obtained from BTHS patients, delinquent CL remodeling was accompanied with mitochondrial accrual of monolysocardiolpin (MLCL), the monodeacylated form of CL. Importantly, we provided evidence that MLCL accumulation could be reversed employing small molecule regulators of calcium independent phospholipase A2, suggesting that in addition to deficient membrane packaging, MLCL amassment was a crucial intracellular lesion in this syndrome. In my current work at the Pacific University School of Pharmacy, I am interested in the development and validation of putative translational therapeutics for Barth Syndrome (BTHS). I will explore the following two broad areas: (1) the role of acute and chronic inflammation in cardiomyopathy and (2) the regulation of mitochondrial calcium in BTHS. For these, I will employ molecular biology, lipidomics and proteomics tools.

Pancreatic Cancer: A recent area of research interest is investigation into the development and progression of pancreatic cancer. Although rarer than other forms of cancer, pancreatic carcinoma has a poor prognosis since it is usually discovered late. Of the many types of pancreatic neoplasia, I am interested in understanding the mechanistic development of pancreatic ductal dysplasia. In particular my emphasis is on the identification of natural compounds that cause apoptosis in pancreatic cancer cell lines. At the Pacific University School of Pharmacy, I aim to explore alterations in intracellular signal transduction pathways downstream of treating cells with natural compounds such as Diindolylmethane (DIM), Neem leaf extracts and other pharmacognostic agents. These exploratory studies will serve to provide preliminary data for translational therapeutic discovery.

Grants and Funding

2010 | National Pancreas Foundation Grant. Title: The role of dendritic cells in the immune progression of pancreatitis to pancreatic cancer. PI: Ashim Malhotra. Award: $50,000; completed 2011

2009 | Barth Syndrome Foundation Grant. Title: The distribution of tafazzin and cardiolpin in the mitochondrial supramolecular complexes – implications for Barth Syndrome. PI: Ashim Malhotra. Award: $24,000; completed 2010

2005 | Eli Lilly. Title: The effect of the anti-cancer drug mechlorethamine on mitochondrial membrane stability. PI:Dipak Haldar. Co-PI:Ashim Malhotra; completed 2006 

2004 | Eli Lilly. Title: Aging process in the mitochondria: effect on membrane structure. PI:Dipak Haldar. Co-PI: Ashim Malhotra; completed 2005

Professional Affiliations

American Association of the Colleges of Pharmacy (AACP )

American Heart Association (AHA)

New York Academy of Sciences (NYAS)

Publications

Book Chapters:

Malhotra, A. "Cardiology Applications in Nanotechnology: Proof of Principle" in Nanotechnology Applications, 2014. IGI Global Publishers.

Khan, F & Malhotra, A. "Introduction to Biochemistry" in Medicinal Chemistry for Pharmacy Students. Khan, F & Phillips, A (under contract, 2014 publication date). Jones and Bartlett Publishing: Boston, Mass.

Malhotra, A & Khan, F. "Pharmacology of Immunosuppressive Agents and Miscellaneous Drugs" in Medicinal Chemistry for Pharmacy Students. Khan, F & Phillips, A (under contract, 2014 publication date). Jones and Bartlett Publishing: Boston, Mass.

Malhotra, A. "Introduction to Pharmacogenomics" in Pharmacotherapeutics for Nurse Practitioner Prescribers, 4thed. Woo, TM & Robinson, ML (under contract, 2015 publication date). FA Davis: Philadelphia, Pa.

Peer Reviewed Journal Articles:

* Denotes Pacific University Student

2014   Malhotra A, Kahlon P*, Donhoe T, Doyle IC.  Pharmacogenomic considerations in the pediatric cardiomyoapthy called Barth Syndrome” in Recent Patents on Biotechnology. Special issue: Current Topics in Pharmacogenomics. In Press.

2014   Turner B, Grover  A, Malhotra A.  “The clinical management of pancreatic cancer” in US Pharmacist.

2011  Acehan D, Malhotra A, Xu Y, Ren M, Schlame M."Cardiolipin affects the supramolecular organization of ATP synthase in mitochondria" in Biophys J. 100 (9): 2184-92.

2011  Bedrosian AS, Nguyen AH, Hackman M, Connolly MK, Malhotra A, Ibrahim J, Cieza-Rubio NE, Henning JR, Barilla R, Rehman A, Pachter HL, Medina-Zea MV, Cohen SM, Frey AB, Acehan D, Miller G. "Dendritic cells promote pancreatic viability in mice with acute pancreatitis" in Gastroenterology. 141 (5): 1915-26

2011  Connolly M, Ayo D, Malhotra A, Hackman M, Ibrahim J, Bedrosian AS, Cieza-Rubio NE, Henning JR, Pachter HL, Frey AB, Miller G."Dendritic cell depletion exacerbates acetaminophen hepatotoxicity" in Hepatology.54 (3): 959-68

2010  Connolly MK, Bedrosian AS, Malhotra A, Henning JR, Ibrahim J, Vera V, Cieza-Rubio NE, Hassan BU, Pachter HL, Cohen S, Frey AB, Miller G. "In hepatic fibrosis, liver sinusoidal endothelial cells acquire enhanced immunogenicity" in J Immunol. 185 (4): 2200-8.

2010  Malhotra A, Edelman-Novemsky I, Xu Y, Ma J, Schlame M, Ren M. "Genetic supressors of Barth Syndrome as potential targets for therapeutic intervention" in 2010.Mitochondrion. 10 (2): 207-208.

2009  Xu Y, Zhang S, Malhotra A, Edelman-Novemsky I, Ma J, Kruppa A, Cernicica C, Blais S, Neubert TA, Ren M, Schlame M."Characterization of tafazzin splice variants from humans and fruit flies" in J Biol Chem.284 (42): 29230-9.

2009  Malhotra A, Xu Y, Ren M, Schlame M."Formation of molecular species of mitochondrial cardiolipin. 1. A novel transacylation mechanism to shuttle fatty acids between sn-1 and sn-2 positions of multiple phospholipid species" in Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 2009.1791 (4): 314-20.

2009  Malhotra A, Edelman-Novemsky I, Xu Y, Plesken H, Ma J, Schlame M, Ren M."Role of calcium-independent phospholipase A2 in the pathogenesis of Barth syndrome" in Proc Natl Acad Sci U S A. 106 (7): 2337-41

2009  Acehan D, Khuchua Z, Houtkooper RH, Malhotra A, Kaufman J, Vaz FM, Ren M, Rockman HA, Stokes DL, Schlame M."Distinct effects of tafazzin deletion in differentiated and undifferentiated mitochondria" in Mitochondrion. 9 (2): 86-95

2009  Connolloy M, Mallen-St. Clair J, Bedrosian A, Malhotra A, Vera V, Ibrahim J, Pachter L, Bar-Sagi D, Frey A, Miller G. “Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor" in J Leuk Bio.87 (4): 713-25.

2006  Xu Y, Malhotra A, Ren M and Schlame M. "The enzymatic function of tafazzin" in J Biol Chem. 281 (51): 39217-24

Office Location: 
Health Professions Building 2 375
Hours: 

By appointment

Area of Study I Teach (Graduate/Professional):