Graduate Students chosen:

Rachel Buchanan (The University of Texas Health Science Center at Houston)

Bioresorbable Putty for Treatment of Osteoporotic Vertebral Compression Fractures

Bio
Rachel Buchanan obtained a B.S. in Biomedical Engineering in May 2009 from Rensselaer Polytechnic Institute. She began her Ph.D. pursuit at The University of Texas at Austin in June 2009. Her studies are under the advisorship of Dr. Mauro Ferrari at the Department of Nanomedicine and Biomedical Engineering at The University of Texas Health Science Center at Houston. She is currently investigating nanostructured scaffolds for musculoskeletal tissue engineering applications.

Abstract
Fragility fractures of the spine or vertebral compression fractures (VCFs) are a major health concern accounting for 547,000 of the 2 million fragility fractures occurring in the U.S. each year, making it the most common site of occurrence. Long term consequences of VCFs are impaired function, decreased quality of life, pulmonary disorders and increased mortality. Current treatments for vertebral compression fractures include the injection of poly(methyl methacrylate) cement into the vertebral body to stabilize the fracture and eliminate associated pain. However, PMMA cement is an insufficient treatment that merely treats the symptoms of the pathology rather than the underlying cause of osteoporotic bone. The ideal treatment would be to revert kyphotic deformity by restoring height and inducing bone regeneration to avoid further progression of the disease. The objective of this study is to create an injectable and biodegradable polymeric scaffold alternative to PMMA cement that will restore both the anatomy and function inherent to healthy trabecular bone. The composite material will contain: a crosslinkable polymer, porous silica nanoparticles, porous silicon microparticles, mesenchymal stem cells and bioactive molecules. The porous silica nanoparticles will contribute mechanical reinforcement and visualization of the injectable polymeric putty that is essential for VCF treatment. Porous silicon microparticles will contribute controlled delivery of bioactive molecules when incorporated into the polymer via a porogen. The putty will crosslink in vivo to initially stabilize the fracture through the enhanced mechanical strength provided by the embedded silica. Once injected, the incorporated porogen will dissolve, thereby creating porosity and releasing the encapsulated cocktail of bioactive molecules and stem cells into the scaffold. The construct is therefore capable of actively promoting rapid bone regeneration while simultaneously restoring essential functionality through degradation of the scaffold and gradual transfer of the mechanical load. This novel bioresorbable putty will not only restore height and stability of the vertebral body for pain relief but rebuild the bone microstructure to the appropriate bone mass and strength that was compromised by osteoporosis.

Laura Carpin (Rice University)

Photoablative Gold Nanoshell Therapy of Chemotherapy-Resistant Cancer Cells

Bio
Laura was born and raised outside of Baltimore, Maryland. She received her bachelor's degrees in Chemical Engineering and Biochemistry from the University of Maryland, College Park in 2005. Laura is currently a student in the Medical Scientist Training Program at Baylor College of Medicine and is pursuing the doctorate portion of her MD/PhD at Rice University in the Bioengineering Department. She is a member of the lab of Dr. Rebekah Drezek, whose lab focuses on the applications of optics and nanotechnology to cancer. Laura's research focuses on gold nanoparticle-mediated photothermal therapy and its applications to breast cancer.

Abstract
Gold nanoshells are very small particles made up of a core, usually silica, and a thin layer of gold on the outside. They have unique optical properties that allow them to either scatter or absorb light, depending on their size, and their gold surfaces easily permit the addition of targeting molecules, such as antibodies. When designed to absorb light in the near-infrared region, a near-infrared laser can be used to heat the nanoshells, killing any cells in the immediate vicinity. We apply this technology to the treatment of chemotherapy resistant breast cancers. Although many advances have been made in treating breast cancer, chemotherapy resistance has prevented true clinical progress in the treatment of advanced cancers. Patients with metastatic breast cancer normally receive chemotherapy as part of their treatment. Often, however, they do not respond to treatment due to the tumor cells developing resistance to the therapeutic agent. One source of chemotherapy resistance is the tumor cells developing an internal resistance mechanism to the chemotherapy drug, as in patients who develop resistance to trastuzumab, a drug used to treat HER2+ breast cancer. Another source of chemotherapy resistance may be a special population of cells known as tumor initiating cells (TICs), which are innately chemotherapy resistant and hypothesized to be a source of metastases and tumor growth. However, many patients have no response to trastuzumab due to their tumor cells having innate resistance. If tumor cells that are resistant to treatment could be targeted and killed in an alternative, physical manner, such as heating, this could significantly slow or halt cancer progression and circumvent the development of drug resistance. By using gold nanoshells to thermally ablate malignant cells, we can target and destroy cancer cells that are otherwise resistant to treatment.

Eric Frey (Rice University)

Unraveling Nanostructures of the Influenza A Virus Using Nanotechnology

Bio
I am a PhD student in the Department of Physics & Astronomy at Rice University, Houston, and a member of Dr. Ching-Hwa Kiang’s group. My research interest is experimental biological physics. I received a B.S. in physics from Miami University (Ohio) in 2008, where I worked in the area of high-pressure biological physics. In 2007, I was awarded the Astronaut Foundation scholarship and the Barry M. Goldwater scholarship.

Abstract
Influenza viruses are efficient nanomachines designed by Nature. They cause a highly contagious respiratory illness and are serious threats to public health. One critical step in infection is the binding of nucleoprotein to single-stranded viral RNA, which forms helical rods 12 nm in diameter called ribonucleoprotein (RNP). What are the interactions holding the RNP structure together, and how strong are they? We are attempting to answer this question by quantifying the mechanical response of influenza A RNP to applied force, using atomic force microscope single-molecule pulling. We will identify the interfaces most critical for RNP stability by examining the consequences of nucleoprotein mutations. Identifying these nucleoprotein interfaces will provide new leads for antiviral drug design. It will also help us understand why Nature has designed the RNP nanorod to solve the problem of packaging nucleic acid for efficient cell delivery. This understanding will be of use in efforts to use viral vectors for gene therapy.

Aman Mann (The University of Texas Health Science Center at Houston)

Bone Marrow Targeted Drug Delivery System for the Treatment of Breast Cancer Bone Metastases

Bio
I am a third year graduate student at the Graduate School of Biomedical Sciences (GSBS) at The University of Texas Health Science Center at Houston (UTHSC-H). Prior to joining the graduate program, I finished my undergraduate degree in Biochemical Engineering from Indian Institute of Technology at Delhi, India. Following my graduation, I carried out cancer research as a Research Scholar for nine months at U.T. M.D. Anderson Cancer Center (UT-MDACC) and this training experience provided me with an opportunity to understand cancer signaling pathways. This experience motivated me to make a solid commitment to pursue cancer research as my career. Currently, I am being mentored by Dr. Mauro Ferrari who serves as the chair of the Department of Nanomedicine and Biomedical Engineering and my current research focus is on developing and validating novel targeting strategies using nanotechnology-based applications for the treatment of metastatic breast cancer. I am strongly committed to breast cancer research, and the research and training resources at UTHSC-H and UT-MDACC, as well as the guidance I will receive from the highly qualified mentors as described in my proposal will greatly benefit me will provide me with an ideal multidisciplinary scientific environment for the proposed study.

Abstract
Bone metastasis is a dreaded diagnosis for a breast cancer patient that causes severe bone pain, pathological fractures, spinal cord compression and hypercalcemia. Bone metastasis frequently occurs in metastatic breast cancer patients (60 to 80 %) and is associated with poor prognosis (5 year survival rate < 20%) and low quality of life. Treatment of bone metastasis remains a challenge due to the presence of hematopoietic stem cells in the bone marrow, and current available treatment options are only palliative. Therefore, there is a critical need to develop effective therapeutic strategies that allows for selective delivery of therapeutic payload to the bone metastases. Our group has developed a multistage drug delivery system that is comprised of biodegradable and biocompatible mesoporous silicon particles (SPP) that can be loaded with therapeutic nanoparticles and released in a timely manner. In addition, the surface of the SPP can be chemically modified with ligand molecules, allowing for a site-specific release of large amounts of payload. Based on the unique functional role of osteoclasts in bone resorption which is the major cause of morbidity and low quality of life associated with breast bone metastasis, we propose to inhibit the osteoclast maturation using micelle formulation of paclitaxel loaded within a bone marrow targeted multistage silicon porous particles (SPP). This delivery strategy based on active targeting is very promising, as a large amount of therapeutic payload will be specifically delivered to the metastatic niches in the bone marrow harboring the osteoclasts.

Srimeenakshi Srinivasan (The University of Texas Health Science Center at Houston)

Design, characterization and validation of multimodal, multifunctional Nanoassemblies for in vivo targeted cancer therapy and diagnostics

Bio
Dr. Srimeenakshi Srinivasan is a graduate student in Dr. Mauro Ferrari’s lab. She received her Baccalaureate in Dental Surgery (BDS) from Tamil Nadu Dr. MGR Medical University, India (2004) during which she secured top rank in Conservative Dentistry, Orthodontics, Periodontics and Prosthodontics and was awarded the Best Final Year BDS for the year 2002-2003. Dr. Srinivasan also made scientific presentations at National conferences like the All India Dental Student’s Conference, Ludhiana and 58^th Indian Dental Conference, Ludhiana. She was awarded MS in Molecular and Cellular Biology at the University of Texas at Dallas (2007). During the period of 2005-2007, she worked under Dr. Stephen Levene and Dr. Rockford Draper doing research on characterization of carbon nanotubes and subcellular nanomanipulations, in their respective labs. She has a scientific article published in Nanotechnology 17 (2006) 4263-4269. Currently she is doing her PhD at the University of Texas Health Science Center, Houston. She underwent training in Dr. Pasqualini’s lab, studying bacteriophages and their applications and then joined Dr. Ferrari’s group to do her research thesis combining the technologies from both labs.

Abstract
An ideal therapeutic drug would be one that reaches the diseased site at maximum concentrations, avoiding the multitude of barriers posed by the vascular system and act only on the target tissue with minimal or no effect of surrounding tissues or even other parts of the body. Our group has designed and characterized one such novel assembly intended for the delivery of imaging agents and therapeutic drugs to diseased site, in particular cancer tissue. These nanoassemblies (NA) are composed of multistage porous silicon (Si) nanocarriers, bacteriophages with recognition moieties and gold (Au) nanoparticles. The accumulation of the system is expected to be preferentially in the tumor site due to the unique margination capabilities of the Si particles, and the recognition moieties on the bacteriophages that home to specific ligands on the surface of tumor cells and associated vascular endothelium. The release of the imaging or therapeutic agents then occurs by passive (degradation of Si particles) or active (NIR/RF triggered) processes. The Au nanoparticles serve as both an imaging contrast as well as a therapeutic modality for photothermal ablation.

New Post Docs chosen:

Dr. Dev Kumar Chatterjee (The University of Texas M.D. Anderson)

Next generation multidimensional chemoradiation therapy

Bio
Dr. Chatterjee completed his medical school training from Calcutta Medical College, a premier medical school in India, where he obtained several awards. He then procured a masters degree in biomedical engineering at the Indian Institute of Technology at Kharagpur, again a flagship engineering institute of the Indian education system. Most recently, he completed his doctoral studies in nanotechnology at the reputed National University of Singapore where he trained under the mentorship of Dr. Zhang, a pioneer in lanthanide nanoparticles’ chemistry and applications. His research interests include nanomedicine in general and biomedical applications of nanoparticles in particular. He has investigated the use of lanthanide based nanoparticles in real-time cellular and molecular imaging and photodynamic therapy, and published several peer-reviewed papers in this field.

His other interests include technopreneurship and commercialization of biomedical advances to reach the bedside. He was part of a start-up company in Singapore for investigating biomedical microdevices, and part of a team that reached the semi-finals of the premier business plan completion in Singapore. He also enjoys sports and reading.

Abstract
Lung cancer accounts for nearly a third of all cancer deaths in men, and a fourth in women in the United States. For a large segment of the lung cancer patients, concurrent chemotherapy and radiotherapy provide the best tumor response, but often such treatment is poorly tolerated because of toxic effects of each modality. Polymeric drug-carrying nanoparticles can be used to localize chemotherapy to cancerous tissues with reduced side effects and better tolerance, but there are no means to control release of the drug to coincide with the radiotherapy. Gold nanoparticles can be used to enhance the effect of radiotherapy at cancer sites by physical and biological dose enhancement, but there are no conventional nanoparticles that ensure both effects. Therefore, three improvements are essential in the field of lung tumor treatment: a) a means to trigger burst release of chemotherapeutic drugs from nanoparticles at the tumor site; b) a means to increase effectiveness of radiation damage to tumors by simultaneous physical and biological dose enhancement; and c) a means to ensure temporal harmony of the two strategies in order to achieve maximum effectiveness with minimum collateral damage.

Here, a proposal is put forward that seeks to ensure coincidental, effective, enhanced and localized activity of chemotherapy and radiotherapy using an engineered nanoconstruct. To solve the problem of combining physical and biological dose enhancements for radiation therapy, we propose the use of gold nanorods, which have sufficient gold content to induce radiation dose enhancement as well as tunable absorption spectra for optical activation of hyperthermic radiosensitization. To enhance the release of drug from nano-carriers at the tumor site, as well as to ensure that this release coincides with radiation therapy, we propose the coating the gold nanorod core with a drug carrying radiation-labile coat. Successful completion of these experiments will conclude our demonstration of enhanced radiation sensitization by thermoradiotherapy (gold nanorod-mediated hyperthermia + gold nanorod-mediated radiation dose enhancement) in conjunction with tumor-localized chemotherapy using an engineered nanoconstruct in an animal model of lung cancer.

Dr. Elvin Blanco (The University of Texas Health Science Center at Houston)

Nested Nanotherapeutics for Enhanced Drug Synergy in Breast Cancer Treatment

Bio
Elvin Blanco received his BS in Biomedical Engineering from Case Western Reserve University (CWRU) in Cleveland, Ohio in 2002. In the same year, he began his graduate training at CWRU in Biomedical Engineering under the mentorship of Dr. Jinming Gao. In 2005 he received his MS in Biomedical Engineering from CWRU and relocated with Dr. Gao’s laboratory to the Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center at Dallas (UTSW). In 2008, he received his PhD in Biomedical Engineering from UTSW. In 2009, Elvin began his postdoctoral training under the mentorship of Dr. Mauro Ferrari at the University of Texas Health Science Center at Houston, working in close collaboration with Dr. Funda Meric-Bernstam in the Department of Surgical Oncology at the University of Texas MD Anderson Cancer Center.

Abstract
Chemotherapy is used as an adjuvant therapy in breast cancer, with current regimens involving the use of a combination of drugs such as doxorubicin, cyclophosphamide, and paclitaxel, all with the hopes of maximizing synergy. However, drug synergy in breast cancer therapy is rarely realized in vivo given the different pharmacokinetic profiles of drugs. Moreover, several limitations to traditional chemotherapy exist in the form of drug resistance, hydrophobicity, and non-specific drug distribution resulting in toxicity. Several breakthroughs in the understanding of underlying molecular mechanisms of tumorigenesis have resulted in the discovery and design of drugs capable of exerting effects on key molecular targets in tumors, ushering in a new trend in chemotherapy. For example, the phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway has been found to be aberrantly activated in breast cancers, resulting in the inability to regulate cell growth and proliferation. Rapamycin hinders cell growth and proliferation by inhibiting mTOR, resulting in G1 cell cycle arrest. The drug has been shown to act synergistically with several well-established anticancer agents in a time- and sequence-dependent fashion. We believe that if multiple drugs are delivered to the tumor, and the same sequence and time of delivery is maintained, an enhanced antitumor efficacy can be achieved.

Dr. Kyle Hammerick (Rice University)

Nanostructured Polymers with MSCs and iPSCs for Pregeneration of Bioactive ECM

Bio
Kyle earned his undergraduate degree at Rice University in Materials Science and Engineering and then pursued a masters degree in Materials Science and Engineering at Stanford University. His work on orthopaedic tissue engineering as a research assistant at the Orthopaedic Research Laboratory at the Stanford School of Medicine piqued his interest in regenerative medicine. Subsequently, he earned his doctorate in Mechanical Engineering from Stanford University, but worked in the field of stem cell biology. Kyle’s dissertation research was primarily on physical regulation of biology and novel mechanisms for controlling adult stem cell fate commitment. His research interests lie in osteogenesis in adult and pluripotent cells. Currently, he is pursuing the use of nanostructures as an exquisitely controllable switch to drive osteogenesis through mechanical regulation of stem cells.

Abstract
As characteristic length scales of structures approach the nanometer regime, interesting and useful phenomena begin to emerge as surface energies dominate material interactions: melting temperatures change, electrical conductivity changes, and even mechanical properties can be altered. We are just beginning to evaluate how we can exploit these often, beneficial properties, to influence and control biology. Nanostructured fibrous cellular substrates have the unique ability to recapitulate the scale and morphology of native bone. The proposed research is aimed at optimizing poly(ε-caprolactone) (PCL) electrospun scaffolds to determine the ideal nanoscale architecture that enhances osteogenic matrix deposition by adult mesenchymal stem cells. Ultimately, these preconditioned scaffold-extracellular matrix constructs will be used to drive in situ differentiation of an induced pluripotent stem cell population devoid of soluble osteogenic factors. The combination of autologous, reprogrammed cell sources with nanostructured biodegradable materials could prove a powerful clinical therapy in the pursuit of viable engineered bone.

Dr. Elizabeth McCullum (Baylor College of Medicine)

De novo Evolution of Anti-breast Cancer Peptide Therapeutics for Nano-based Drug Delivery

Bio
Elizabeth O. McCullum is a Birmingham, AL native and a 2003 graduate of Judson College in Marion, AL. She earned her Ph.D. in chemistry from Arizona State University in 2009 and recently assumed a postdoctoral fellowship appointment at Baylor College of Medicine in the Department of Pediatrics and the Texas Children’s Cancer Center Dept. of Hematology/Oncology.

Dr. McCullum is the recipient of the 2009 Ladies Auxiliary to the Veteran’s of Foreign Wars Postdoctoral Fellowship to support her project on breast cancer research. During her graduate school tenure, she was the author of several peer-reviewed articles pertaining to the use alternative nucleic acid systems for use in bionanotechnology and expanding the function of DNA polymerases for use in molecular biology. While at BCM, she plans to apply an in vitro selection technique to identify peptides that inhibit the formation of the tripartite protein complex Cohesin which will potentially lead to targeted cell death. And, subsequently hopes couple these peptides to a well-developed protein scaffold for “nano-drug delivery” to specific breast cancer cells. This research effort contributes to the ongoing investigation of selectively identifying peptide therapeutics to exclusively combat proliferating oncogenic mammary cells.

Upon completion of her appointment, Dr. McCullum hopes to blend her passion for healthcare promotion, disease prevention and biomedical research in a transitional role at the forefront of health policy and regulatory affairs.

Abstract
Several specific molecular networks mediate the cellular proliferation of tumorogenic cells. One signaling pathway of interest is the transition from metaphase to anaphase which is dependent on cleavage of the Cohesin protein complex by Separase, an endopeptidase. A normal transition allows the protein complex to form, sister chromatid cleavage and the onset of anaphase. However, failure to properly assemble or maintain the integrity of this complex results in the premature separation of chromatids (PCS), mitotic arrest and apoptosis in cultured cells. This research effort will focus on the development of peptide inhibitors that would disrupt sister chromatids cohesion and induce apoptotic cell death in tumor tissue. We hypothesize that cohesin Rad21, a proapoptotic protein that is over-expressed in breast cancer cells, will serve as the specific target for the induction of apoptosis in the cohesin-disrupted tumor. Rational design, based on evolutionary sequence conservation, of Rad21 mimics targeting the chromosomal cohesin complex will induce PCS in oncogenic cells. The peptides will compete with the assembly of the normal cohesin subunits to block complex formation, which will trigger the cells to apoptose. The potential advantages provide an area of promising therapeutics for antitumor effects when coupled with chemotherapy at the point of early detection.

Senior Post Docs chosen:

Dr. Rita Serda (The University of Texas Health Science Center at Houston)

Monitoring targeted delivery and therapeutic efficacy of multistage vectors by scanning electron microscopy

Bio
I received my Ph.D. in Biomedical Sciences from the University of New Mexico, Department of Biochemistry and Molecular Biology, in Albuquerque, NM in December 2006. My mentor was John Omdahl, a giant in stature and heart, and a victim to cancer in February, 2005. During graduate school, I worked as an Instructor at Central New Mexico Community College and I was a tutor for the medical school. I received an NIH NRSA Predoctoral Fellowship, the Edmund J & Thelma W Evans Charitable Trust Scholarship, and I was a New Mexico Alliance for Hispanic Education Scholar for three years. In January of 2007, I joined Mauro Ferrari’s Group at the Institute of Molecular Medicine at the University of Texas Health Science Center, Division of Nanomedicine. In 2007, I was awarded a Department of Defense Multidisciplinary Postdoctoral Award, and the following year I received the Federation of the American Societies for Experimental Biology (FASEB) Professional Development and Enrichment Award. Most recently, I am the recipient of a Senior Postdoctoral Alliance for NanoHealth Fellowship. On a personal note, I am a single parent with two wonderful boys, Cory and Joshua, and I have three sisters, Diane, Andrea, and Alicia.

Abstract
Nano-engineered delivery systems are emerging as powerful tools for the systemic delivery of therapeutic molecules and contrast agents for cancer applications. Barriers to systemic delivery of therapeutics include uptake by professional phagocytes, enzymatic degradation, and physical barriers, such as the vascular endothelium and cellular membranes. To overcome these and other barriers, we have assembled a multistage delivery system which targets the tumor in steps, each step conquering a specific biological barrier. The first stage vector is targeted to molecules over or uniquely expressed in the tumor neovasculature while subsequent stage vectors, which are released in a time-controlled fashion dependent on degradation of the first stage particle or released by triggered opening of the porous matrix (e.g. pH or protease driven), target successive barriers. The Alliance for NanoHealth project will focus on applications for breast cancer therapy with an emphasis on vasculature targeting and selective delivery of therapeutics to the tumor microenvironment. The overall goal of this initiative is to visually monitor cellular interactions with targeted multistage vectors at nanoscale resolution and to monitor delivery of therapeutic agents by examining morphological changes in the tumor using scanning electron and confocal microscopy.

Dr. Arturas Ziemys (The University of Texas Health Science Center at Houston)

Assessment of chemotherapy drug transport by silicon nanovectors

Bio
Born in Lithuania in 1974, I acquired a bachelors degree in Biological sciences and masters degree in Biotechnology and Molecular Biology. I defended my PhD thesis in Biomedical Sciences and Molecular Biophysics. I was an Associated Professor and staff scientist in Vytautas Magnus University and Institute of Biochemistry (Lithuania). I twice received an award from the National Academy of Sciences, Lithuania. I did my Postdoctoral training at Ohio State University in protein denaturation and liquid interface structure at ambient and high pressures. At present I am doing my postdoctoral training in the Department of Nanomedicine and Bioengineering (nBME), UTHSC, in nanoscale drug transport and nanofluidics. I am Co-author of an awarded project in the Rice business competition for microgravity that granted space experiments for nanotechnologies. I have expertise in computational simulations and experimental techniques.

Abstract
The emergent properties of materials and devices fabricated with critical dimensions in the nanoscale present significant opportunities in the fields of medicine and biotechnology. The cancer treatment remains the leading priority and advances in nanotechnology bring new targeted and local drug delivery opportunities to increase efficacy. However, very limited solubility of chemotherapy drugs together with new transport physics at nanoscale pose challenges. This study aims to study the chemotherapy drug transport at nanoscale and what effects has different nanochannel environment to drug transport and delivery using silicon nanovectors. The research will use modeling and experimental methods to understand the nanoscale transport of drugs and provide understanding of surface chemistry effects.