We have several areas of research interest broadly in the area of immunomodulation using micro/nanoparticles and other carrier systems. This can include development of traditional vaccines, therapeutic autoimmune vaccines and classic drug delivery platforms targeted to bacterial, viral or parasitic host cells. To this end, we also seek to develop new materials and platforms optimal for use in modulating immune responses as well as developing scalable production of micro/nanoparticles.
We are interested in studying diabetic vasculopathies. Patients with type 2 diabetes mellitus or metabolic syndrome have aggressive forms of vascular disease, possessing a greater likelihood of end-organ ischemia, as well as increased morbidity and mortality following vascular interventions. Our long term research aims to change the way we treat arterial disease in diabetes by:
- Understanding why arterial disease is more aggressive in diabetic patients, with a focus in redox signaling in the vasculature.
- Developing targeted systems using nanotechnology to locally deliver therapeutics to the diseased arteries.
What if you can target and deliver a drug directly to the side of disease in the body? It is possible, when you use smart living creatures pro-inflammatory response cells, such as monocytes, T-lymphocytes or dendritic cells. You can load these cells with the drug and inject these carriers into the blood stream. They will migrate to the inflammation site (for example, across the blood brain barrier) and release the drug. Thus, you can reduce the inflammation and protect the cells (for example, neurons) in patients with Parkinson’s and Alzheimer diseases.
Pathobiology & Translational Science
Dr. Benhabbour’s academic research focuses on development of novel tunable delivery platforms and polymer-based devices to treat or prevent a disease. Her work combines the elegance of organic and polymer chemistry with the versatility of engineering and formulation development to design and fabricate efficient and translatable nanocarriers and drug delivery systems for cancer treatment and HIV prevention.
Dr. Benhabbour has also Founded her startup company Anelleo, Inc. (AnelleO) in 2016 to develop the first 3D printed intravaginal ring as a platform technology for women’s health.
Current technologies in development in Dr. Benhabbour’s Lab include:
– 3D Printed intravaginal ring technology: A) Multipurpose prevention technology (MPT) for prevention of HIV/STIs and unplanned pregnancy.
– Polymer based ultra-long-acting injectable implant for HIV prevention and treatment.
– Combinatory chitosan/cellulose nanocrystals thermoresponsive hydrogel system: A) Sub-Q or intraosseous injectable for treatment of osteoporosis; B) Bio-ink for 3D bioprinting; C) Scaffold for stem cell delivery (e.g. iNSCs for treatment of post-surgical glioblastoma.
– Mucoadhesive thin film for treatment of vulvodynia.
– Targeted nanoparticles and hydrogel scaffolds for treatment of NSCLC.
Biochemistry & Biophysics
The Button lab in the Department of Biochemistry and Biophysics is part of the Marsico Lung Institute. Our lab is actively involved in projects that are designed to define the pathogenesis of muco-obstructive pulmonary disorders and to identify therapies that could be used to improve the quality of life in persons afflicted by these diseases. In particular, our research works to understand the biochemical and biophysical properties of mucin biopolymers, which give airway mucus its characteristic gel-like properties, and how they are altered in diseases such as Asthma, COPD, and cystic fibrosis.
The direct fabrication and harvesting of monodisperse, shape-specific nano-biomaterials are presently being designed to reach new understandings and therapies in cancer prevention, diagnosis and treatment. Students interested in a rotation in the DeSimone group should not contact Dr. DeSimone directly. Instead please contact Chris Luft at email@example.com.
The broad aim of research in the Fenton Laboratory is to develop and evaluate synthetic drug delivery platforms to treat neurodegenerative disorders in the brain using RNA therapeutics. RNA therapeutics represent a particularly promising class of therapeutics for neurodegenerative management given their ability to tune levels of specific protein expression in living systems. For example, protein downregulation can be achieved by administering short interfering RNAs (siRNAs); alternatively, proteins can be upregulated by messenger RNA (mRNA) administration. Despite this promise, fewer than 0.05% of the world’s clinically approved drugs are RNA therapeutics, and their translation to neurodegenerative disorders in the brain warrants further study at the fundamental and clinical levels.
To address these challenges, our group focuses on the discovery and development of molecular carriers and technology platforms to improve the targeting, safety, and efficacy of RNA drugs within target cells. Specifically, our group leverages an interdisciplinary approach to develop lipid nanoparticles (LNP) as well as soft matter hydrogel platforms that can serve as carrier systems and/or drug delivery models for RNA drugs. Further, our group also explores the development of technological platforms to further expand the potential of RNA drugs within resource limited settings. Lastly, given that mRNA drugs can be engineered to encode for virtually any polypeptide or protein based antigen, our group also aims to leverage our platformable LNP technologies for the study and prevention of cancers and infectious disease. In undertaking such an approach, the goal of our research is to equip students with fundamental skillsets for the development of next generation drugs while simultaneously developing clinically-relevant carrier platforms and technologies for the study, prevention, and treatment of human disease.
My lab focuses on developing bioinspired molecular constructs and material platforms that can mimic proteins and be programmed to respond to stimuli resulting from biomolecular recognition. Major efforts are directed to design peptide- and nucleic acid-based scaffolds or injectable nanostructures to create artificial extracellular matrices that can directly signal cells.
Genetics & Molecular Biology
My research focus centers on retinal gene/drug therapy using nanotechnologies. My laboratory is interested in developing gene therapies for inherited blinding diseases and eye tumors. We are particularly interested in understanding the gene expression patterns that are regulated by the cis-regulatory elements. We utilize compacted DNA nanoparticles which have the ability to transfer large genetic messages to overcome various technical challenges and to appreciate the translational potential of this technology. This multidimensional technology also facilitated targeted drug delivery. Currently, we are working on the design and development of several specific nano formulations with targeting, bioimaging and controlled release specificities.
Microbiology & Immunology
Our lab works with adeno-associated viral vectors for both the characterization of vector and host responses upon transduction and as therapeutic agents for the treatment of genetic diseases. In particular, we tend to focus on the 145 nucleotide viral inverted terminal repeats of the transgenic genome and their multiple functions including the replication initiation, inherent promoter activity, and stimulation of intra/inter molecular DNA repair pathways. The modification of the AAV ITRs by synthetic sequences imparts unique functions/activities rendering these synthetic vectors perhaps better suited for therapeutic applications.
In our lab we develop novel polymer based drug delivery systems and nanomedicines incorporating small molecules, DNA and polyptides to treat cancer, neurodegenerative and other CNS-related disorders.
The Knight group focuses on designing novel macromolecular materials with functions inspired by biological systems. These materials will generate platforms of new biomimetic polymeric architectures addressing growing concerns in treating, diagnosing, and preventing human disease. This research bridges the fields of chemical biology and polymer chemistry using characterization and synthetic tools including polymer and solid-phase synthesis and nanomaterial characterization. Specific project areas include: (1) developing a new class of peptide-polymer amphiphiles inspired by metalloproteins, (2) designing well-defined polymer bioconjugates for biosensing, and (3) evolving functional biomimetic polymers.
Our dynamic group are broadly involve in three topics: (i) prevention of infectious diseases by harnessing interactions between secreted antibodies and mucus, (ii) immune response to biomaterials, and (iii) targeted delivery of nanomedicine. Our group was the first to discover that secreted antibodies can interact with mucins to trap pathogens in mucus. We are now harnessing this approach to engineer improved passive and active immuniation (i.e. vaccines) at mucosal surfaces, as well as understand their interplay with the mucosal microbiome. We are also studying the adaptive immune response to polymers, including anti-PEG antibodies, and how it might impact the efficacy of PEGylated therapeutics. Lastly, we are engineering fusion proteins that can guide targeted delivery of nanomedicine to heterogenous tumors and enable personalized medicine.
My research has focused on developing new radio-chemistry, imaging probes, and therapeutic approaches including nanomedicine for various diseases. Most importantly, we have the culture of forming an active collaboration with people in different field. With a cGMP lab located within our facility, we are also experienced on developing lead agents and translate it to clinic.
The research interests of the Liu Lab are in functional proteomics and biopharmaceuticals. Currently we are working on the following projects: (1). Using systems biology approaches to decipher the signaling pathways mediated by disease-related proteases such as caspases and granzymes and by post-translationally modified histones. We address these problems by performing functional protein selections using mRNA-displayed proteome libraries from human, mouse, Drosophila, and C. elegans. (2). Developing novel protein therapeutics and nucleic acid therapeutics that can be used in tumor diagnosis, treatment, and nanomedicine. We use various amplification-based molecular evolution approaches such as mRNA-display and in vivo SELEX to develop novel single domain antibody mimics on the basis of very stable protein domains or to generate aptamers on the basis of nuclease-resistant nucleic acids, that bind to important biomarkers on the surface of cancer cells. We further conjugate these biomarker-binding affinity reagents to small molecule drugs or nanoparticles for targeted delivery of therapeutic agents. (3). Identifying the protein targets of drugs or drug candidates whose action mechanisms are unknown. We combine molecular proteomic and chemical biology approaches to identify the protein targets of drugs whose target-binding affinities are modest.
Pecot Lab: Therapeutic RNAi to Teach Cancer how to “Heal” and Block Metastatic Biology
Synopsis: The Pecot lab is looking for eager, self-motivated students to join us in tackling the biggest problem in oncology, metastases. An estimated 90% of cancer patients die because of metastases. However, the fundamental underpinnings of what enables metastases to occur are poorly understood. The Pecot lab takes a 3-pronged approach to tackling this problem: 1) By studying the tumor microenvironment (TME), several projects are studying how cancers can be taught to “heal” themselves, 2) By studying how cancers manipulate non-coding RNAs (micro-RNAs, circle RNAs, snoRNAs, etc) to promote their metastatic spread, and 3) We are investigating several ways to develop and implement therapeutic RNA interference (RNAi) to tackle cancer-relevant pathways that are traditionally regarded as “undruggable”. Students joining the lab will be immersed in the development of novel metastatic models, modeling and studying the TME both in vitro and in vivo, using bioinformatic approaches to uncover mechanistic “roots”, and implementation of therapeutic approaches
Our lab is broadly interested in utilizing high resolution 3D printing to develop novel drug delivery carriers for the treatment of cancer and infectious diseases. Current research interests lay in manufacturing biodegradable porous hydrogel scaffold implants for cell/drug delivery for the treatment of recurrent brain cancer. We are actively investigating biomaterial properties for passive cell/drug loading into scaffolds as well as developing materials and methods to support conjugation strategies for actuated release mechanisms.
Dr. Rizvi’s expertise is in imaging and therapeutic applications of light, bioengineered 3D models and animal models for cancer, and targeted drug delivery for inhibition of molecular survival pathways in tumors. His K99/R00 (NCI) develops photodynamic therapy (PDT)-based combinations against molecular pathways that are altered by fluid stress in ovarian cancer. He has co-authored 46 peer-reviewed publications and 5 book chapters with a focus on PDT, biomedical optics, and molecular targeting in cancer.
Pathobiology & Translational Science
Dr. Troester’s research focuses on stromal-epithelial interactions, genomics of normal breast tissue, breast cancer microenvironment, and molecular pathology of breast cancer progression. She is a Co-Investigator on the Carolina Breast Cancer Study (CBCS), a resource including breast tumors from thousands of African American women, and she is PI of the Normal Breast Study (NBS), a unique biospecimen resource of normal tissue from women undergoing breast surgery at UNC Hospitals. Dr. Troester has extensive experience in integrating multiple high dimensional data types. She is chair of the Normal Breast Committee for the Cancer Genome Atlas Project where she is leading coordination of histology, copy number, mutation, methylation, mRNA and microRNA expression data. She has more than a decade of experience working with genomic data and molecular biology of breast cancer progression and has published many papers in the area of breast cancer subtypes, breast microenvironment, and stromal-epithelial interactions. She has trained four postdocs, 12 predoctoral students and several undergraduates.
Applied Physical Sciences
The Yan lab works at the interface of material science, photonics, and biology. We synthesize metal, metal oxide and upconversion nanoparticles for biophotonics and biomedicine applications. We use holographic optical tweezers and atomic force microscope (AFM) to trap and manipulate single nanoparticles, and use them as probes to study nano-bio interactions, including biosensing, bionanomechanics and cell biology. We conduct these studies with a customized multi-modal correlative optical system that combines the nanomanipulation module with advanced optical microscopy and spectroscopy techniques.