Profile: Malavosklish (Liz) Bikram

Malavosklish (Liz) Bikram
Malavosklish (Liz) Bikram, Ph.D.
Assistant Professor of Pharmaceutics
Department of Pharmacological and Pharmaceutical Sciences
UH College of Pharmacy
Texas Medical Center Campus, Room 516
1441 Moursund St.
Houston, TX 77030

832-842-8385 
832-842-8305 (fax)
mbikram@uh.edu

Education

Postdoctoral Fellow (Bioengineering), Rice University, Houston, Texas
Ph.D., Pharmaceutics & Pharmaceutical Chemistry, University of Utah, Salt Lake City, Utah
B.S., Biochemistry & Biological Sciences, University of Denver, Denver, Colo.

Research Interests

I. Development of Intelligent Nonviral Gene Delivery Systems for Disease Modulation

The focus of this research project is to design, synthesize, and fully characterize novel biomaterials that can respond to specific stimuli in its environment so as to ultimately modulate a disease towards a clinical treatment. In order to accomplish this, we need to understand the biochemical environment of a disease and translate its unique pathophysiology into a property that can be integrated into a delivery system that will enable the system to actuate upon entry into that narrowly defined space. To this end, we have developed unique linear L-lysine modified copolymers (LLCs) that contain disulfide bonds along the backbone and the natural amino acid lysine as reducible polymers for the delivery of nucleic acids. Thus, the polyplexes formed between the copolymers and the nucleic acids are completely stable in the extracellular space, whilst the system spontaneously decomposes in a reducing environment such as the intracellular compartments of cells. This intelligent system can subsequently be tuned to many disease states and can deliver both RNA as well as DNA cargoes to targeted cells.

II. Development of Nanocarriers for Drug Delivery

The goal of this research project is to develop controlled targeted liposomal systems that are targeted to a disease for optimal release of drug and/or therapeutic molecules. These nanocarriers are currently designed for the delivery of drugs aimed at treating infectious diseases such as invasive pulmonary aspergillosis (IPA). Our first step was to understand the mechanism of how liposomal carriers are able to interact with Aspergillus fumigatus hyphae and then use this knowledge to further improve the design of the carriers. We have found that liposomal systems including stealth liposomes interact with these fungi via β-glucans that are present on the growing tips and septa of the hyphae to modulate drug delivery. We will now use these findings to engineer liposomal carriers to further increase the targeting of the system to areas of pulmonary infections so as to increase the therapeutic efficacy of the delivery carrier.

III. Development of Biocompatible & Bioresponsive MRI Contrast Agents

This project is initially divided into 2 separate projects with the final goal of combining the research into composite materials.

In the first project, we are interested in developing biocompatible magnetic resonance imaging (MRI) contrast agents for early detection of breast and ovarian cancer. To this end, we have functionalized superparamagnetic iron oxide (SPIO) nanoparticles with dual bioresponsive elements specific to the tumor microenvironment that would facilitate cell targeting and specific uptake into cancer cells. This accumulation of nanoparticles can result in high specificity and sensitivity of the contrast agent in order to serve as an early detection probe. In addition, the versatility of the platform technology enables easy tailoring to different types of cancers and can thus result in broad patient applicability.

In the second project, we have developed biocompatible MRI contrast agents that contain typical but toxic heavy metals such as gadolinium ions. These ions are non-natural toxic elements that can undergo transmetallation within the body in order to release these metals into the body from their chelated parent molecules. However, these metals produce excellent T1 relaxations that make them beneficial for imaging of internal compartments in the body. Thus, to increase the biocompatibility of these metal ions, whilst preserving their imaging benefits, we have doped SPIO nanoparticles with gadolinium and coated the resulting particles with a metal layer of either gold or an alloy of gold and silver. Consequently, we have developed both T1 and T2 contrasts agents that offer the advantages of gadolinium.

Patents

Bikram M. Ultrasmall Superparamagnetic Iron Oxide Nanoparticles and Uses Thereof. U.S. Patent No.: 8, 147, 803.

Research Grants

U.S. Department of Defense: Bioresponsive Nanoparticles as Magnetic Resonance Molecular Probes.

Texas Higher Education Coordinating Board, Advanced Research Program: Stealth Targeted Magnetic Resonance Molecular Probes for Cancer Detection

Selected Publications

Gheorghe DE, Cui L, Karmonik C, Brazdeikis A, Penaloza JM, Young JK, Drezek RA, Bikram M. Gold-silver alloy nanoshells: a new candidate for nanotherapeutics and diagnostics. Nanoscale Res Lett. 2011 Oct 13;6:554.

Nounou MI, Emmanouil K, Chung S, Pham T, Lu Z, Bikram M. Novel reducible linear L-lysine-modified copolymers as efficient nonviral vectors. J Control Release. 2010 May 10;143(3):326-34.

Mody VV, Nounou MI, Bikram M. Novel nanomedicine-based MRI contrast agents for gynecological malignancies. Adv Drug Deliv Rev. 2009 Aug 10;61(10):795-807. Review.

Bikram M, West JL. Thermo-responsive systems for controlled drug delivery. Expert Opin Drug Deliv. 2008 Oct;5(10):1077-91. Review.

Bikram, M., Gobin, A.M., Whitmire, R.E. and West, J.L. (2007). Temperature-sensitive hydrogels with SiO2-Au nanoshells for controlled drug delivery. J. Control. Release. 123:219-227.

Bikram, M., Fouletier-Dilling, C., Hipp, J.A., Gannon, F., Davis, A.R., Olmsted-Davis, E.A. and West, J.L. (2007). Endochondral bone formation from hydrogel carriers loaded with BMP2-transduced cells. Ann. Biomed. Eng. 35:796-807.

Janat-Amsbury, M.M., Yockman, J.W., Lee, M., Kern, S., Furgeson, D.Y., Bikram, M., and Kim, S.W. (2005). Local, non-viral IL-12 gene therapy using a water-soluble lipopolymer as carrier system combined with systemic paclitaxel for cancer treatment. J. Control. Release. 101: 273-285.

Bikram, M., Lee, M., Chang, C.W., Janat-Amsbury, M.M., Kern, S.E., and Kim, S.W. (2005). Long-circulating DNA-complexed biodegradable multiblock copolymers for gene delivery: degradation profiles and evidence of dysopsonization. J. Control. Release. 103: 221-233.

Lee, M., Bikram, M., Oh, S., Bull, D.A., and Kim, S.W. (2004). Sp1-dependent regulation of the RTP801 promoter and its application to hypoxia-inducible VEGF plasmid for ischemic disease. Pharm. Res. 21: 736-741.

Janat-Amsbury, M.M., Yockman, J.W., Lee, M., Kern, S., Furgeson, D.Y., Bikram, M., and Kim, S.W. (2004). Combination of local, nonviral IL12 gene therapy and systemic paclitaxel treatment in a metastatic breast cancer model. Mol. Ther. 9: 829-836.

Bikram, M., Ahn, C.-H., Chae, S.Y., Lee, M., Yockman, J.W., and Kim, S.W. (2004). Biodegradable poly(ethylene glycol)-co-poly(L-lysine)-g-histidine multiblock copolymers for nonviral gene delivery. Macromolecules. 37: 1903-1916.

Lee, M., Rentz, J., Bikram, M., Han, S., Bull, D.A., and Kim, S.W. (2003). Hypoxia-inducible VEGF gene delivery to ischemic myocardium using water-soluble lipopolymer. Gene Ther. 10: 1535-1542.

Presentations & Abstracts

Bikram M., Nounou M.I., Cui L., Gheorghe D.E., Lorenz B., Karmonik C. Nanomaterials For Biomedical Applications. Podium presentation. Proceedings of ASME 2010 First Global Congress on NanoEngineering for Medicine and Biology, NEMB2010, February 7-10, 2010 Houston, TX, USA.

Bikram M. Biocompatible Materials for Biomedical Applications. Podium presentation. Society for Biomaterials: Biomaterials Day at Texas A & M University. February 22, 2010, College Station, TX.

Nounou M.I., Emmanouil K., Chung S., Pham T., Lu Z., Bikram M. Novel Lysine-Based Bioreducible Nonviral Gene Delivery System. Podium presentation. AAPS National Biotechnology Conference. May 16-19, 2010. San Francisco, CA.

Nounou M.I., Emmanouil K., Chung S., Pham T., Lu Z., Bikram M. Novel Reducible L-Lysine Copolymers (LLCs) for Nonviral Gene Delivery. The 37th Annual Meeting and Exposition of the Controlled Release Society. July 10-14, 2010. Submitted. Portland, OR.

Cui L., Gheorghe D.E., Penaloza J.M., Pan Y., Bikram M. Development of Tumor-Targeting MRI Contrast Agent for Imaging. The 37th Annual Meeting and Exposition of the Controlled Release Society. July 10-14, 2010. Submitted. Portland. OR.

M. Bikram., Gheorghe D.E., Penaloza J.M., Lorenz B, Karmonik C. Metal-Alloy Nanoshells as New Nanotherapeutic and Diagnostic Agents. The 37th Annual Meeting and Exposition of the Controlled Release Society. July 10-14, 2010. Submitted. Portland, OR.

Nounou M.I., Emmanouil K., Chung S., Pham T., Lu Z., Bikram M. Efficient DNA Delivery Using Novel Bioreducible Linear L-Lysine Modified Copolymers (LLCs). Poster Presentation. Alliance for NanoHealth (ANH) Investigators Meeting, February 23, 2010. Houston, TX.

Cui L., Gheorghe D.E., Mogri E., Nguyen D., Yuli Pan, Bikram M. Novel Bioresponsive MRI Contrast Agent for Imaging. Poster Presentation. Alliance for NanoHealth (ANH) Investigators Meeting - February 23, 2010. Houston, TX.

Nounou M.I., Emmanouil K., Chung S., Pham T., Lu Z., Bikram M. Novel L-Lysine Reducible Copolymer For Efficient Nonviral Gene Delivery. Poster Presentation. The American Society of Gene & Cell Therapy 13th Annual Meeting. Accepted. San Diego, CA. May 17-22, 2010. Washington, D.C.

Lili Cui, Gheorghe D.E., Mody V.V., Karmonik C. Bikram M. Development of MMP-Specific MRI Contrast Agent for Ovarian Cancer. Poster Presentation. Meeting: 239th ACS National Meeting & Exposition - March 21-25, 2010, San Francisco, CA.

Gheorghe D.E., Penaloza J.M., Karmonik C., Drezek R.A., Bikram M. Gold-Silver Alloy Nanoshells: A New Candidate for Nanotherapeutics and Diagnostics. Poster Presentation. 239th ACS National Meeting & Exposition, March 21-25, 2010, San Francisco, CA.

Gheorghe D.E., Mody V.V., Penaloza J.M., Lorenz B., Karmonik C., Bikram M. Synthesis And Characterization Of Gold Alloy Nanoshells On Gd-Doped Iron Oxide Nanoparticles. Biomedical Engineering Society annual meeting. October 7-10, 2009, Pittsburgh, PA.

Nounou M.I., Mody V.V, Emmanouil K., Pham T., Lu Z., Bikram M. Design, Synthesis And Characterization Of Novel Lysine-Based Bioreducible Nonviral Gene Delivery System. Poster Presentation. Biomedical Engineering Society annual meeting. October 7-10, 2009, Pittsburgh, PA.

Mody V.V., Nounou M.I., Cui L., Karmonik C., Lorenz B., Bikram M. Development Of MMP-Specific MRI Contrast Agent For Ovarian Cancer. Poster Presentation. Biomedical Engineering Society annual meeting. October 7-10, 2009, Pittsburgh, PA.

Nounou M.I., Mody V.V, Emmanouil K., Pham T., Lu Z., Bikram M. Novel Lysine Based Bioreducible Non Viral Gene Carrier System: Synthesis, Characterization And In Vitro Evaluation. Poster Presentation. American Society of Gene Therapy 12th Annual Meeting. Accepted. San Diego, CA. May 27-30, 2009.

Nounou M.I., Mody V.V, Emmanouil K., Pham T., Lu Z., Bikram M. Efficient DNA Delivery Using Novel Bioreducible Linear L-Lysine-Modified Copolymers (LLC). Poster Presentation. Recent Advances in Drug Delivery Systems 14th International Symposium. Salt Lake City, UT. February 15-18, 2009.

Mody V.V., Nounou M., Karmonik C., Bikram M. Synthesis Of Dual Bioresponsive Ultrasmall Superparamagnetic Iron Oxide Nanoparticles As MR Contrast Agents And Evaluation Of Its Cytotoxicity In Vitro. Poster Presentation. The Houston Society for Engineering in Medicine and Biology. Houston, TX. March 19-20, 2009.

Gheorghe D.E., Mody V.V., Bikram M. Synthesis And Characterization Of Gold Alloy Nanoshells On Gd-Doped Iron Oxide Nanoparticles. Poster Presentation. The Houston Society for Engineering in Medicine and Biology. Houston, TX. March 19-20, 2009.

Nounou M.I., Mody V.V, Emmanouil K., Pham T., Lu Z., Bikram M. Synthesis and Characterization Of Novel Bioreducible Linear Disulfide Copolymers (LDC) For Non-Viral Gene Delivery. Oral Presentation. The Houston Society for Engineering in Medicine and Biology. Houston, TX. March 19-20, 2009.

Mody V.V., Nounou M., Karmonik C., Bikram M. Development of Tumor-Targeted MRI Contrast Agents for the Early Detection of Ovarian Cancer. Poster Presentation. Controlled Release Society. New York, NY. July 12-16, 2008.

Bikram M, Mody V.V., Nounou M., Karmonik C. Tumor-specific MRI Contrast Agents for Ovarian Cancer. Poster Presentation. Gordon Research Conference. Big Sky, MT. August 24-29, 2008.

Mody V.V., Nounou M., Karmonik C., Bikram M. Development of Tumor-Targeted MRI Contrast Agents for the Early Detection of Ovarian Cancer. Poster Presentation. Controlled Release Society. New York, NY. July 12-16, 2008.

Mody V.V., Abdelraouf K., Nounou M., Karmonik C., Bikram M. Synthesis and Characterization of Bioresponsive Ultrasmall Paramagnetic Iron Oxide Nanoparticles as MR Contrast Agents. Oral Presentation. The Houston Society for Engineering in Medicine and Biology. Houston, TX. February 7-8, 2008.

Bikram M., Fouletier-Dilling C., Shafer J.A., Hipp J.A., Davis A.R., Olmsted-Davis E.A., West J.L. Bone Formation from Hydrogel Carriers Loaded with Adenovirus Transduced Cells Expressing BMP-2. Poster Presentation. Recent Advances in Drug Delivery Systems 13th International Symposium. Salt Lake City, UT. February 26-28, 2007.

Bikram M., Gobin A., Whitmire R.E., West J.L. Modulated Protein Release from Hydrogel Drug Reservoirs. Oral Presentation. American Chemical Society 62nd Southwest Regional Meeting. Houston, TX. October 20, 2006.

Bikram M., Fouletier-Dilling C., Shafer J.A., Hipp J.A., Davis A.R., Olmsted-Davis E.A., West J.L. Ectopic Bone Formation from Hydrogel Carriers Loaded with BMP-transduced Cells. Oral Presentation. Society For Biomaterials 2006 Annual Meeting and Exposition. Pittsburgh, PA.

Bikram M., Gobin A.M., Whitmire R.E., Sershen S.R., West J.L. Temperature-sensitive Hydrogels with SiO2-Au Nanoshells for Controlled Protein Delivery. Oral Presentation. Society For Biomaterials 2006 Annual Meeting and Exposition. Pittsburgh, PA.

Lab Alumni

Postdoctoral Fellows

Dr. Vicky Mody (2007 – 2009), Assistant Professor of Medicinal Chemistry, Appalachian College of Pharmacy

Dr. Dana E. Gheorghe (2008 – 2009), University of Houston, TX Ctr Superconductivity at UH

Graduate Students

Mohamed Ismail Nounou (2007 – 2011), Postdoctoral Fellow, Texas Tech University Health Sciences Center

Lili Cui (2008 – 2011), Pharmacological & Pharmaceutical Sciences, University of Houston

Undergraduate Research Students

2006-2007 Van Ho, University of Houston

2008 Zhuoyuan Lu, Ph.D. Candidate, University of Houston

Summer 2008 Stephen Potter, Alliance for Graduate Education and the Professorate (AGEP), Lone Star College

2008-2009 Ife Bamgbose, University of Houston

2008-2009 Kalyopy Emmanouil, University of Houston

2008-2009 Rithu Johnson, University of Houston

2008 An Dao, University of Houston

2008 Ngoc Thuy, University of Houston

2008 Ejiro Umaka, University of Houston

2007-2008 Linda Barrera, University of Houston

Summer 2008 Sue Dinh, University of Houston

Summer 2008 Sylvester Hawkins, Mississippi State College

2009 Samuel Chung, University of Houston

2009 Toan Nguyen, University of Houston

2009 Jose Penaloza, University of Houston

2009 Ebrahim Mogri, University of Houston

2008–2009 Thu Pham, University of Houston

2009 Dan Nyugen, University of Houston

2009 Kim Anh Pham, University of Houston

2009- 2010 Yuli Pan, University of Houston

Summer 2009 Amaris Fuentis, University of Houston

2010 Amber Shahid, University of Houston

2010 Flor Mendes, University of Houston

2010–2011 Nga Le, University of Houston

2010 Rezwana Zahir, University of Houston

2010 Sahr Ahmed, University of Houston

2010–2011 Sameer Saifuddin, University of Houston

Spring 2011–present Ekim Ekinci, University of Houston

Fall 2011–present Christina Baroi, University of Houston

Fall 2011–present Joey Almaguer, University of Houston

Summer 2011 Neyaz Mohammadi, Trinity College, San Antonio

2012 Abidemi Oreoluwa, University of Houston