Troy Rohn, Ph.D.

Research update:

Recently, I have become interested in finding novel treatments for anxiety due to a personal reason: About three years ago, I was diagnosed with anxiety that was amplified during the Covid-19 epidemic. I have had counseling and I take medication daily, including the standard long-term medications known as SSRIs. Even my dog Bailey helps me a ton. About this time, I was contacted by John Mee to see if I was interested in building a new biotech company. John is the current CEO of Cognigenics and at that time the company had no capital or data, but they had a great idea and a blue-ribbon team. I joined the team and became director of their preclinical studies. RCA-101 was our first asset and is an unusual biologic “drug” that utilizes CRISPR/Cas9. CRISPR is the new, precision gene-editing tool poised to cure many disorders and diseases in the 21st century. We proposed to permanently lower anxiety by targeting the serotonin receptor (5HT-2A) gene using CRISPR. This receptor has been known for decades to be linked to anxiety. Today, 39 million Americans suffer from anxiety disorders and ~30-40% do not respond to current treatments including SSRIs, Zoloft, and Cipramil. A few weeks ago, our proof-of-concept paper was published in PNAS Nexus, a top-tier journal. Currently, this paper is in the top 5% of all research outputs as scored by Altermic (Altmetric tracks millions of published articles) and is one of the most-read articles at PNAS Nexus. In less than two weeks since it has been published, it has already been viewed over 3,200 times and our findings have generated a buzz on the internet:

One piece of compelling data we obtained was demonstrating a similar efficacy of RCA-101 to diazepam (Valium). RCA-101 was delivered as a single intranasal dose on day 1, and five weeks later (equivalent to ~5 human years) anxiety was assessed. This was in contrast to diazepam which was given acutely and anxiety was measured 1 hour later (Figure 1). We also showed that after a single intranasal delivery of the CRISPR/Cas9, cargo was distributed throughout the brain (Figure 2)

graph — Figure 1: Anti-Anxiety. RCA-101 treated mice (red) performed comparably to diazepam (1mg/kg valium) with no side effects compared to the control

brain scan image — Figure 2. Representative, low-field immunofluorescence sagittal image following treatment, fixation in formalin, and immunolabeling using a specific antibody against green-fluorescence protein (GFP). GFP-positive neurons positively transfected with guide RNA were identified in most brain regions including the olfactory bulb (OB), cortex, cerebellum, and numerous sub-cortical areas including the interpeduncular nucleus (IPN), a major connectome for stress-mediated pathways.

These data we believe put us on track for human clinical trials shortly. For me, having anxiety and trying to find new treatments for anxiety has been a personal journey that has been very rewarding as a result of my connection both in research and my own anxiety. I have even got a tattoo recently (my first and only)!

Professor, Department of Biological Sciences

Year arrived at BSU: 2000

Mailing Address:
Department of Biology
Boise State University
Boise, ID 83725-1515
Office Location: Science Building, Room 117
Office Number: 208-426-2396
Lab Location: Science Building, Room 216
E-Mail Address: trohn@boisestate.edu

Academic Degrees

Troy Rohn graduated in 1990 from the University of California at Davis with a B.S. in Physiology. He received his Ph.D. in Pharmacology from the University of Washington, Seattle in 1994. His interests include the role of ApoE4 in Alzheimer’s disease. Dr. Rohn had several Postdoctoral stints including two-plus years living in Paris, France, one year at Montana State University in Bozeman, Montana, and two years at UC Irvine. He has obtained extramural funding continuously since his arrival at BSU including grants from NIH, AFAR, and AHAF. Dr. Rohn recently was awarded a 3-year renewal of his NIH NIA R15 grant he has held since 2013.

Teaching

BIOL 442: This is a molecular neurobiology course for undergraduate and graduate students. Topics covered are all aspects of neuronal function at the molecular level. A discussion of several neurodegenerative diseases including Parkinson’s, Alzheimer’s, and Schizophrenia are just a few of the diseases covered.

BIOL 431: This is a general pharmacology course for undergraduate and graduate students. Topics include pharmacokinetics and pharmacodynamics. All major drug classes are covered in this course including drugs that affect the heart, brain, vasculature, and all other major organ systems.

BIOL 100 at Boise State University (Electronic): This is a non-major course covering all aspects of biology (taught online in the summers).

BIOL 320: A cell biology course that represents a core requirement for all biology majors.

UF 100: Brain Matters: A survey of the brain covering behavior, plasticity, genetics, and many diseases and disorders.

RESEARCH INTERESTS

The Rohn lab has a long-standing interest in understanding the molecular underpinnings of Alzheimer’s disease (AD). During the progression of Alzheimer’s disease, many brain cells die particularly in the area of the hippocampus. Because the hippocampus is an area of the brain involved in memory, AD is primarily a disease where afflicted individuals lose their capacity for memory and eventually other important cognitive skills involved in executive functions.

The primary focus of my lab currently is understanding how inheritance of the apolipoprotein E4 (APOE4) gene greatly enhances dementia risk. Although it is well established that inheritance of the APOE4 allele increases the risk of AD approximately tenfold, the mechanism of how this protein contributes to AD pathogenesis remains unknown. We have recently discovered that a fragment of ApoE4 in the human AD brain when produced is toxic and inflammatory.

The APOE4 gene represents the single greatest risk factor for AD, however, how the expressed protein actually contributes to dementia risk is not well understood. This diagram shows a myriad of possible actions of how harboring the gene may contribute to AD pathology

We are excited to currently be examining the in vivo effects of ApoE fragments in zebrafish a new model system for the lab where we have recently shown that following treatment of embryos with an amino-terminal fragment of ApoE4, leads to toxicity and effects on the heart including a significant decrease in heart rate. We have also generated a mutant zebrafish strain that specifically expresses this ApoE4 fragment and are in the process of characterizing these fish through molecular techniques and behavioral analyses.

Figure showing the expression of an amino-terminal fragment of ApoE4. Representative expression of mCherry (red) in the brain and notochord following injection into one-cell stage zebrafish. The expression of enhanced green fluorescent protein under the cardiac myosin light chain 2 promoter (green), allows for easy screening of zebrafish for the mutant ApoE4 gene. These pictures were obtained by a current undergraduate student, Alex LaFollette who is working in the lab as a B2B student.

RECENT PUBLICATIONS (selected from 75 total)

H-index 39

Troy T. Rohn, Dean Radin, Tracy Brandmeyer, Barry J. Linder, Emile Andriambeloson, Stéphanie Wagner, James Kehler, Ana Vasileva, Huaien Wang, John L. Mee and James H. Fallon. (2023). Genetic modulation of the HTR2A gene reduces anxiety-related behavior in mice. PNAS Nexus, Volume 2, Issue 6, June 2023, pgad170, https://doi.org/10.1093/pnasnexus/pgad170

McCarthy, M.M., Hardy, M.J., Leising, S.E., LaFollette, A., Stewart, E.S., Cogan, A.S., Sanghal, T., Matteo, K., Oxford, J.T., and Rohn T.T. (2022). An amino-terminal fragment of apolipoprotein E4 leads to behavioral deficits, increased PHF-1 immunoreactivity, and mortality in zebrafish. PLOS One Dec 15;17(12):e0271707. doi: 10.1371/journal.pone.0271707. eCollection 2022

Rohn, T.T., Beck, J.D., Galla, S.J., Isho, N.F., Pollock, T.B., Suresh, T., Kulkarni A., Sanghal, T. and Hayden, E.J. (2021). Fragmentation of apolipoprotein E4 is required for differential expression of inflammation and activation related genes in microglia cells. Int J Neurodegener Dis. (2021),4(1): 020.doi: 10.23937/2643-4539/1710020. Epub 2021 Sep 10.

Rohn, T.T. (2021). The new FDA-approved drug for Alzheimer’s disease, aducanumab, and what patients should know. J Alzheimers Dis Parkinsonism, DOI: 10.4172/2161-0460.s5.1000019

Pollock, T.B., Isho, N.F., Day, R.J., Suresh, T., Cholico, G.N., Stewart, E.S., McCarthy, M.M. and Rohn, T.T. (2020). Transcriptome analyses in BV2 microglial cells following treatment with amino-terminal fragments of apolipoprotein E. Front. Aging Neurosci., 13 August 2020 | https://doi.org/10.3389/fnagi.2020.00256 | https://doi.org/10.3389/fnagi.2020.00256

Oxford, A.E., Stewart, E.S., Rohn T.T. (2020). Clinical Trials in Alzheimer’s Disease: A Hurdle in the Path of Remedy. Int J Alzheimers Dis. Apr 1;2020:5380346. doi: 10.1155/2020/5380346. eCollection 2020.

Pollock, T.B., Mack, J.M., Day, R.J., Isho, N.F., Brown, R.J., Oxford, A.E., Morrison, B.E., Hayden, E.J. and Rohn T.T. (2019). A fragment of apolipoprotein E4 leads to the downregulation of CXorf56, a novel ER-protein, and activation of BV2 microglial cells. Oxidative Medicine and Cellular Longevity. Volume 2019, Article ID 5123565. https://doi.org/10.1155/2019/5123565

Rohn, T.T., Kim, N., Isho, N.F. and Mack, J.M. (2018). The potential of CRISPR/Cas9 gene editing as a treatment strategy for Alzheimer’s disease. J Alzheimers Dis Parkinsonism. 8(3). Pii: 439. Doi: 10.4172/2161-0460. Epub 2018 May 31.

Love, J.E., Day, R.J., Gause, J.W, Brown, R.J., Pu, X., Theis, D.I., Caraway, C.A., Poon, W.W., Rahman, A.A., Morrison, B.E., and Rohn T.T. (2017). Nuclear uptake of an amino-terminal fragment of apolipoprotein E4 promotes cell death and localizes within microglia of the Alzheimer’s disease brain. Int J Physiol Pathophysiol Pharmacol: 9(2): 40-57

RESEARCH OPPORTUNITIES

The lab is not accepting any positions for the 2022-23 academic year for both undergraduate and graduate students

OTHER ACTIVITIES

Scientific director of preclinical studies for Cognigenics

Cognigenics has developed novel methods for treating a wide range of mental health challenges, from generalized anxiety and chronic depression to cognitive impairment. Our patent-pending technology precisely targets the neurological causes of mental health issues using the gene-editing tool, CRISPR/Cas9. We anticipate that this novel, targeted approach will deliver high efficacy with little or no side effects. My role is to guide the preclinical studies testing this technology using both in vitro and in vivo model systems.

Instructor for biomedical molecular courses in neurobiology for high school students

Working with the Rosetta Institute of Biomedical Research, we provide advanced classes for high-achieving high school/middle school students interested in pursuing a career in medicine or related fields. We offer a variety of workshops related to molecular medicine – Molecular Biology of Cancer, Molecular Neuroscience, Molecular Immunology, Molecular Biology of Aging, Medicinal Chemistry, Medical Bioinformatics, Introduction to Cellular and Molecular Medicine, Emerging Pathogenic Viruses, Cancer Research, Immunology Research, and Biomedical Research. These summer workshops are taught at UC Berkeley and UC San Diego.

Associate Editor

Associate Editor for the scientific journal, Frontiers in Dementia

Associate Editor for the scientific journal, Frontiers in Aging Neuroscience

Anxiety, CRISPR, and Serotonin

Research update

Recently, I have become interested in finding better treatments for anxiety. Why? About three years ago, I was diagnosed with anxiety, which really became worse during the Covid-19 epidemic. I have had counseling and I take medication daily. Even my dog Bailey helps me a ton. Interestingly, about the same time, I was contacted by John Mee to see if I was interested in building a new biotech company. John is the current CEO of Cognigenics and at that time the company had no capital or data, but they had a great idea and a blue-ribbon team. I joined the team and became director of their preclinical studies. RCA-101 was our first asset and is an unusual biologic “drug” that utilizes CRISPR/Cas9. CRISPR is the new, precision gene-editing tool poised to cure many disorders and diseases in the 21st century. We proposed to permanently lower anxiety by targeting the serotonin receptor (5HT-2A) gene using CRISPR. This receptor has been known to be linked to anxiety for decades. Today, 39 million Americans suffer from anxiety disorders and ~30-40% do not respond to current treatments including SSRIs, Zoloft, and Cipramil the standard long-term medications. A few weeks ago, our proof-of-concept paper on this concept was published in PNAS Nexus, a top notch journal. Currently, this paper is in the top 5% of all research outputs as scored by Altermic (Altmetric tracks millions of published articles) and is one of the most-read articles at PNAS Nexus. In less than two weeks since it has been published, it has already been viewed over 3,200 times and our findings have generated a buzz on the internet:

Here are images showing proof-of-concept data. One important finding was the similar efficacy of RCA-101 to Valium (diazepam), a gold standard for lowering anxiety.

These data we believe put us on track for human clinical trials shortly. For me, having anxiety and trying to find new treatments for anxiety has been a personal journey that has been very rewarding. As a result of my connection both in research and my own anxiety.