“Nanofluidic Technologies for Cell and Drug Delivery on-Earth and in Space”

Abstract:
Unprecedented development in controlled delivery systems have allowed for mimicking of endocrine glands responsive to biological cues for the treatment of hormonal and metabolic disorders. In this context, micro- and nanofluidic systems represent unique platforms that can be exploited to recapitulate organ functions or enable superior control of drug administration.
This talk will provide an overview of the nanofluidic nanotechnologies under development and translation in our laboratory for the controlled delivery of therapeutics and for the transplantation of endocrine cell for the treatment of chronic pathologies. Emphasis will be given to technologies developed for HIV Pre-exposure Prophylaxis, obesity and metabolic syndrome, intratumoral cancer immunotherapy as well as diabetes. Additionally the work developed in the HMRI’s Center for Space Nanomedicine will be presented specifically for what pertains the development and testing of nanotechnologies and rodent studies on board of the International Space Station (ISS).

“Replaying Human Neurophysiology and Disease with Microphysiological Systems and iPSC Technologies”

Abstract: Neurodegenerative diseases of both familial and idiopathic origin are recognized as having genetic contributors that may present before birth. However, the identity of disease initiating genes and their contribution to cellular dysfunction leading to clinical presentation is poorly understood. Cedar-Sinai’s Tissue Chip team has developed two highly functional and scalable microphysiological models containing spinal cord cells (SC-Chip) to study sporadic ALS and midbrain cells (mBrain-Chip) to study sporadic Parkinson’s Disease. Both Chip models integrate a human microfluidic vascular channel that can interact with patient stem cell derived neural tissue and exhibit blood brain barrier properties. Cedars-Sinai’s Induced Pluripotent Stem Cell (iPSC) Core has generated large cohorts of patient and non-diseased iPSC lines for use in in vitro disease research and target discovery. The main objective of this work is to develop robust and reproducible human vascularized models of spinal cord and midbrain tissue, determine live and molecular signatures that indicate a diseased state, and test efficacy and blood brain barrier characteristics of candidate therapeutics. To determine disease Chip biomarkers, a comprehensive array of live and molecular assays were applied to Chip microtissues. These include whole genomic, transcriptomic, proteomic, metabolomic, and electrophysiological assays. Pilot disease cohorts of 10 patient lines were screened for candidate biomarkers in patient Chips using RNA-Seq, proteomics, calcium Imaging, and staining. Putative molecular biomarkers were identified as ALS and PD specific in the spinal cord Chip and midbrain Chip respectively.

"The Role of Tumor Hypoxia in the Immune Response to Solid Tumors"

Abstract:

Tumor hypoxia is thought to promote the recruitment and T-cell suppressive activity of polymorphonuclear myeloid derived suppressor cells (PMN-MDSCs). However, the net effect of hypoxia on PMNs within the overall context of the tumor microenvironment remains incompletely understood. To address this issue, we administered in vivo respiratory hyperoxia as a novel way to alleviate tumor hypoxia. Applying this approach to a clinically relevant model of endometrial cancer revealed tumor hypoxia as a potent inhibitor of anti-tumor PMN function. Moreover, hypoxia relief dramatically reduced uterine tumor burden in a PMN-dependent, but T cell-independent fashion. In addition to revealing novel aspects of direct PMN effector mechanisms in cancer, I will also discuss my futures directions that support the emerging possibility that relief of hypoxia is an attractive adjunct modality in cancer immunotherapy.

“Bioengineered Oral Medicine to Treat Obesity and Diabetes”

Abstract:

Obesity is considered a strong factor in many chronic diseases, including heart disease, cancer, and diabetes. Along with genetics, consumption of excessive fat and cholesterol-rich food are the primary causes of obesity. However, despite of an alarming emergency there has been little progress made developing medications for controlling obesity, conveniently and effectively.

In this seminar, I will talk about various approaches of treating type 2 diabetes and obesity using oral formulations such as ionic liquid that prevents the fat from penetrating through the intestinal membrane. In our recent study we have observed that a regular oral dose of ionic liquid may result less body weight gain compared with the control/untreated rats. On the same line, we have developed an oral formulation to deliver DNA encoded-glucagon like peptide-1 to treat T2D, shows significant reduction of body weight and blood glucose level in rat model.