Morteza Mahmoudi, PhD
Biomedical Investigator, Center for Nanomedicine and Department of Anesthesiology | Brigham and Women’s Hospital
Instructor in Anesthesia | Harvard Medical School
Dr. Mahmoudi is a biomedical investigator with a multidisciplinary background in nanomedicine, bioengineering, sensor array, and cardiac cellular biology. His specific research interest is controlling nano-bio interfaces to develop new nano-based therapies for prevention/treatment of life-threatening conditions such as cardiomyopathy, cancer, and neurodegenerative diseases. He and his colleagues have developed several approaches/assays to probe fundamental cell/molecular-nanoparticle interactions, including cell toxicity, cellular labeling, protein corona, personalized protein corona, and metabolome corona (“corona” refers to a coating of various proteins and metabolomes on the surface of nanoparticles). Dr. Mahmoudi has a productive track record of multidisciplinary collaboration, so far yielding ten patents, five books, and over 170 publications with more than 13,500 citations and an h-index of 56.
A. Development of (nano)Structured Materials for Regenerative Medicine.
Heart failure is a disease state that begins with injured myocardium, causing subsequent deterioration of the heart’s function and the dilation of its chambers. Heart failure is the leading cause of hospital admission worldwide, and over 5 million people currently suffer from this condition in the US. Unlike many other organs, the adult human heart has limited capability for self-repair. Despite advances in clinical trials, the mortality rate associated with heart failure remains high; and there is still no definitive treatment for this disease. The field therefore urgently needs an alternative efficient therapeutic approach. For the last 5 years, we have been actively working on developing nano-based strategies to introduce novel therapeutic approaches for efficient heart regeneration.
- Wei K, Serpooshan V, Hurtado C, Diez-Cuñado M, Zhao M, Maruyama S, Zhu W, Fajardo G, Noseda M, Nakamura K, Tian X, Liu Q, Wang A, Matsuura Y, Bushway P, Cai W, Savchenko A, Mahmoudi M, Schneider MD, van den Hoff MJ, Butte MJ, Yang PC, Walsh K, Zhou B, Bernstein D, Mercola M, Ruiz-Lozano P*. Epicardial FSTL1 reconstitution regenerates the adult mammalian heart. Nature. (2015);525(7570):479-485. PMID: 26375005.
- Serpooshan V, Mahmoudi M*, Zhao M, Wei K, Sivanesan S, Motamedchaboki K, Malkovskiy AV, Goldstone AB, Cohen JE, Yang PC, Rajadas J, Bernstein, D, Woo YJ, Ruiz-Lozano, P*. Protein Corona Influences Cell–Biomaterial Interactions in Nanostructured Tissue Engineering Scaffolds. Advanced Functional Materials. (2015);25(28):4379-89.
- Mahmoudi M, Tachibana A, Goldstone AB, Woo YJ, Chakraborty P, Muth KL, Foote CS, Piecewicz S, Barrozo JC, Wakeel A, Rice BW, Bell III CB, Yang PC*. Scientific Reports. (2016); 6:26960. DOI: 10.1038/srep26960.
- Mahmoudi M*, Yu M, Serpooshan V, Wu JC, Langer R, Lee RT, Karp JM, Farokhzad OC*. Multiscale technologies for treatment of ischemic cardiomyopathy. Nature Nanotechnology. (2017);12(9):845-855. PMID: 28875984.
B. Understanding the Implications of the Protein Corona at the Interface of Nanoparticles and Biological Fluids.
It is now well accepted that we require a fuller understanding of all major interactions at nano-bio interface to design safe, reliable, and high-yield nanoparticles (NPs) for specific biomedical purposes. To that end, extensive studies have been undertaken to probe every relevant factor at the nano-bio interface. Since 2011, the main goal of my international collaborative research has been to identify and introduce to the scientific community important “hidden factors” factors at the nano-bio interface (e.g., the effect of nanoparticles on environmental health, the concept of Personalized Protein Corona and immune response). These findings may contribute substantially to accelerating the progress of nanoparticle technologies from bench discoveries to clinical use.
- Mahmoudi M*, Lynch I, Ejtehadi MR, Monopoli MP, Bombelli FB, Laurent S. Protein-Nanoparticle Interactions: Opportunities and Challenges. Chemical Reviews. (2011);111(9):5610. PMID: 21688848.
- Mahmoudi M*, Lohse S, Murphy CJ, Montazeri A, Fathizadeh A, Suslick, K.S*. Variation of Protein Corona Composition of Gold Nanoparticles Following Plasmonic Heating. Nano Letters. (2014);14 (1):6-12. PMID: 24328336.
- Bigdeli A, Palchetti S, Pozzi D, Hormozi-Nezhad MR, Baldelli Bombelli F, Caracciolo G*, Mahmoudi M*. Exploring Cellular Interactions of Liposomes Using Protein Corona Fingerprints and Physicochemical Properties.ACS Nano. (2016);10(3):3723-37. PMID: 26882007.
- Bertrand N, Grenier P, Mahmoudi M, Lima E, Appel E, Dormont F, Lim J, Karnik R, Langer R, Farokhzad OC*. Mechanistic understanding of in vivo protein corona formation on polymeric nanoparticles and impact on pharmacokinetics. Nat Commun. 2017; 8, 777. PMID: 28974673.*Corresponding Investigator
C. Development of Sensor Array for Identification and Discrimination of Nanoparticles and Biomolecules.
Array based sensing platforms has emerged a powerful approach toward the detection of wide range of biomolecules. Based on cross-responsive sensor elements, these systems aim to produce composite responses unique to each biomolecule. For the first time in the field, we have developed a sensor array for identification and discrimination of nanoparticles with wide range of physicochemical properties. We have also used sensor array platform for detection of various biomolecules including neurotransmitters.
- Askim JR, Mahmoudi M, Suslick KS*. Optical sensor arrays for chemical sensing: the optoelectronic nose. Chemical Society Reviews. (2013);42(22): 8649-8682. PMID: 24091381.
- Ghasemi F, Hormozi-Nezhad MR*, Mahmoudi M*. A colorimetric sensor array for detection and discrimination of biothiols based on aggregation of gold nanoparticles. Analytica Chimica Acta. (2015);882(1):58-67. PMID: 26043092.
- Ghasemi F, Hormozi-Nezhad MR*, Mahmoudi M*. Identification of catecholamine neurotransmitters using fluorescence sensor array. Analytica Chimica Acta. (2016);917(1):85-92. PMID: 27026604.
- Mahmoudi M*, Lohse S, Murphy CJ, Suslick KS*. Identification of Nanoparticles with a Colorimetric Sensor Array. ACS Sensors. (2016);1(1):17–21.
D. Design of Cell-imprinted Smart Nano-patterned Substrates for Controlling Stem Cell Differentiation Toward a Variety of Mature Cells.
Stem cells have enormous potential therapeutic effects in catastrophic diseases such as cancer, cardiovascular, and neurodegenerative diseases. Substrates with various micro- and nanotopographies have been intensively used to control the differentiations of stem cells. We developed a potentially reliable, reproducible, and cost-effective method for controlling the fate of stem cells by using both micro- and nano-patterned substrates that biomimic cell shapes. These substrates are expected to have a positive translational impact, as they will introduce a novel, chemical-free bioengineering approach for differentiation of stem cells into mature functional cells, for both drug screening and therapeutic applications in a variety of diseases.
- Mahmoudi M*, Bonakdar S, Shokrgozar MA, Aghaverdi H, Hartmann R, Pick A, Witte G, Parak WJ*. Cell-Imprinted Substrates Direct the Fate of Stem Cells. ACS Nano. (2013);7(10):8379-84. PMID: 24059979.
- Mashinchian O, Bonakdar S, Taghinejad H, Satarifard V, Heidari M, Majidi M, Sharifi S, Peirovi A, Saffar S, Taghinejad M, Abdolahad M, Mohajerzadeh S, Shokrgozar MA, Rezayat SM, Ejtehadi MR, Dalby MJ, Mahmoudi M*. ACS Applied Materials & Interfaces. (2014);6(15):13280-13292. PMID: 24967724.
- Mashinchian O, Turner LA, Dalby MJ, Laurent S, Shokrgozar MA, Bonakdar S, Imani M, Mahmoudi M*. (2015). Regulation of stem cell fate by nanomaterial substrates. Nanomedicine. (2015);10(5):829-847. PMID: 25816883.
- Bonakdar S, Mahmoudi M*, Montazeri L, Taghipoor M, Bertsch A, Shokrgozar MA, Sharifi S, Majidi M, Mashinchian O, Hamrang Sekachaei M, Zolfaghari P, Renaud P*. ACS Applied Materials & Interfaces. (2016); 8 (22):13777-13784. PMID: 27196338.
E. Fabrication of Novel Nanoparticles to Combat Antibacterial Resistance.
The combination of patients with poor immune systems, prolonged exposure to anti-infective drugs, and cross-infections has given rise to antibiotic resistance, i.e., nosocomial infections with highly resistant pathogens. After extensive research, we prepared different types of engineered multimodal NPs that are completely compatible with human cells. These NPs comprised a magnetic core and a silver ring with a ligand gap and produced high-yield antibacterial effects and eradication of bacterial biofilms. I served as the primary or corresponding author in all the following studies.
- Mahmoudi M*, Serpooshan V. Silver-coated engineered magnetic nanoparticles are promising for the success in the fight against antibacterial resistance threat. ACS Nano. 2012;6(3):2656-64. PMID: 22397679.
- Hajipour MJ, Fromm KM, Ashkarran AA, de Aberasturi DJ, de Larramendi IR, Rojo T, Serpooshan V, Parak WJ, Mahmoudi M*. Antibacterial properties of nanoparticles. Trends in Biotechnology. 2012;30(10):499-511. PMID: 22884769.
- Ashkarran AA1, Ghavami M, Aghaverdi H, Stroeve P, Mahmoudi M*. Bacterial effects and protein corona evaluations: crucial ignored factors in the prediction of bio-efficacy of various forms of silver nanoparticles. Chemical Research in Toxicology. (2012);25(6):1231-1242. PMID: 22551528.
- Gupta A, Saleh NM, Das R, Landis RF, Bigdeli A, Motamedchaboki K, Campos AR, Pomeroy K, Mahmoudi M*, Rotello VM*. Synergistic antimicrobial therapy using nanoparticles and antibiotics for the treatment of multidrug-resistant bacterial infection. Nano Futures. (2017);1(1): 015004.