Our lab is interested in using the designer DNA binding proteins such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and Zinc Finger proteins to develop novel gene and (epi)-gene editing tools for in vivo therapeutics. We apply design principles of synthetic biology to develop controllable genetic circuits and interface with gene therapies for better controllability and safety upon the clinical translations. In this line, our lab has a 3-tier research program:
- Synthetic Biology: We are interested in designing new genetic circuits that confer new behaviors in mammalian cells. Along this notion, we are interested in genetic circuits that can modulate immune response or the genetic circuits that can modulate the function of the gene editors. We apply these tools both in cells and in animal models.
- In vivo gene and (epi)gene therapies: using different delivery systems such as nanoparticles and Adeno-associated viruses (AAV) we are interested in applying CRISPR-based editors to understand tissue biology and modulate the course of diseases, with specific attention to immune response. We are interested to develop and compare different editors for more efficacious therapies, interested to modulate epigenetic codes to change the course of diseases, and develop strategies to counteract immune reaction against gene editors, viral therapies, infectious viruses or chronic inflammatory conditions.
- Human microphysiological systems that can report on immune response to and toxicity following the application of gene editors to human tissues are crucial in developing clinical gene editors. We work with Liver on Chip platform, a 3D perfusable system that allows us to develop and maintain human liver tissue over extended period of time. We use patient-specific cells to assemble immune-competent liver tissues in this platform and analyze their response to gene editing events through high throughput assays such as transcriptomics, genomics and Luminex assays. The goal is to develop biomarkers and predict response to gene editing in human tissues.
In addition, Dr. Kiani is co-producing a documentary film titled "The Human Game" about the future of humans in the era of genomics. She directs "Tomorrow.life" an initiative with a mission to expand public engagement with science through connecting scientists and people with stories with filmmakers. Therefore, we are interested to hear from those who would also like to get involved in this area of activity.
- Ferdosi SR, Ewaisha R, Moghadam F, Krishna S, Park JG, Ebrahimkhani MR, Kiani S*, Anderson K*. Multifunctional CRISPR/Cas9 with engineered immunosilenced human T cell epitopes. Nat Commun. 2019 Apr 23;10(1):1842. (*co-corresponding authors). PMID: PMID: 31015529.
- Yeo NC, Chavez A*, Lance-Byrne A, Chan Y, Menn D, Milanova D, Kuo C, Guo X, Tung A, Cecchi Rj, Tuttle M, Lim Et, Pradhan S, Davidsohn N, Ebrahimkhani M.R, Collins JJ, Lewis N, Kiani S*, Church G*. An enhanced CRISPR repressor for targeted mammalian gene regulation. (*co-corresponding authors) Nature Methods 2018 Aug;15(8):611-616. PMID: 30013045.
- Menn DJ, Pradhan S, Kiani S*, Wang X*. Fluorescent Guide RNAs Facilitate Development of Layered Pol II-Driven CRISPR Circuits. ACS Synth Biol. 2018 Aug 17;7(8):1929-1936. (*co-corresponding authors). PMID: PMID: 30021068.
- Guye P*, Ebrahimkhani MR*, Kipniss N, Velazquez JJ, Schoenfeld E, Kiani S, Griffith LG, Weiss R. Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6. Nat Commun. 2016 Jan 6;7:10243. (*Equal Contribution). PMID: 26732624. Contributed to imaging, hematopoiesis studies (colony formation assays) and writing and editing of manuscript.
- Kiani S, Chavez A, Tuttle M, Hall RN, Chari R, Ter-Ovanesyan D, Qian J, Pruitt BW, Beal J, Vora S, Buchthal J, Kowal EJ, Ebrahimkhani MR, Collins JJ, Weiss R, Church G. Cas9 gRNA engineering for genome editing, activation and repression. Nat Methods. 2015 Nov;12(11):1051-4.
- Kiani S, Beal J, Ebrahimkhani MR, Huh J, Hall RN, Xie Z, Li Y, Weiss R. CRISPR transcriptional repression devices and layered circuits in mammalian cells. Nat Methods. 2014 Jul;11(7):723-6.
- Hockemeyer D, Wang H, Kiani S, Lai CS, Cost GC, Zhang L, Santiago Y, Miller JC, Orlando SJ, Lam S, Vincent AV, Hinkley SJ, Rebar EJ, Gregory PD, Urnov FD, JaenischR. Genetic engineering of human ES and iPS cells using TALE nucleases. Nat Biotechnol. 2011 Jul 7;29(8):731-4.
- Kiani S, Valizadeh B, Hormazdi B; Samadi H, Najafi T, Samini M; Dehpour AR. Alteration in Male Reproductive System in Experimental Cholestasis: Roles For Opioids and Nitric Oxide Overproduction. Eur J Pharmacol. 2009 Aug 1; 615(1-3):246-51. PMID: PMID: 19445924.