Essentially Me - A biographical sketch

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Essentially Me

Many times a day I realize how much my own outer and inner life is built upon the labors of my fellow men, both living and dead, and how earnestly I must exert myself in order to give in return as much as I have received.

Einstein, 1930

Hello, I’m so glad you found this page. My name is Khris. The day of this writing is Apr 20, 2023, and it’s my 39th birthday. I have decided to start this professional site to host ideas and projects that I work on. I have a number of posts in the works that are based on some of my doctoral work. Oh, I have a Ph.D. from the University of California, Los Angles, in the field of Molecular, Cellular, and Integrative Physiology. My area of expertise is in visual neuroscience. My doctoral work investigated molecular mechanisms of photon detection and processing in the mammalian rod visual pathway (Griffis, 2022).

As a vision scientist, I gained skills and experience that opened my understanding of the world, made me a critical thinker, an experimentalist, a leader, an observer, a listener, and a lecturer. I was able to utilize my passions to discover new insights into how our eyes capture the world. I gained experience in technical fields such as statistics, machine learning, data science, dynamical modeling, computer science, electrical engineering, robotics, optics, lasers, and remote sensing. These topics were in addition to the core of my physiological study, which focused heavily on all of neuroscience, from dissections and live imaging to spike sorting and modeling. I also have a wealth of hands-on experience in the wet lab from working with biologically hazardous agents to immuno-chemistry and cell culture. I’ve picked up quite a few tools over the decades, and I’m not done yet.

I am always eager to learn, to educate, to explore the universe, to collaborate, to investigate a thing from every conceivable angle, and to think deeply (sometimes about nothing at all). My most favorite time is spent with my family, outside somewhere, where my two young boys can explore, ask questions, and seek out answers (even if just dreaming up an answer). I’m using this site as a professional bookshelf, but that doesn’t mean there won’t be stories about my personal life. I hope you will check back and see if any of the posts I make in the future make any impact on your life.

Cheers,

Khris

My Scientific Journey

Following my undergraduate degree in Physiological Science (UCLA), I joined the field of neurodegenerative repair, focusing on spinal-cord injury research in the lab of Patricia E. Phelps at UCLA. Beginning in 2011, I focused primarily on the potential benefit of olfactory ensheathing cells (OECs) as an in vitro model of spinal cord injury, and I collaborated on 3 projects assessing the therapeutic effects of OEC engraftments on neural regeneration. In 2013, I began the Master of Science degree in the Department of Integrative Biology and Physiology at UCLA and was able to continue my work in neural repair.

Throughout my tenure in the Phelps lab, I had the opportunity to familiarize myself with several biological tools, including bench work from PCR, western-blot, and immunohistochemistry to cell imaging, cell culture, histology, and cryostat slicing. I managed upwards of 4 rodent colonies as the principle lead of animal husbandry, where I selectively maintained the colonies based on a desired level of expression of transgenic DNA, which I assessed by biochemical methods, e.g., by PCR. I worked closely with the UCLA Department of Laboratory Animal Medicine as the first line of vetinary needs for these colonies. Employing my love for statistics, and my hobby of computer science1, I developed novel analysis methods with Python, R, and MATLAB, to assess the extent of neural circuitry regeneration after spinal transection from electromyographical, transcranial, and spinal epidural electrical recordings. I took advantage of the opportunity to deepen my understanding of electronic circuits, and how they parallel with biological signals, by working with post-doctoral researchers in Dr. Reggie Edgerton’s lab at UCLA and our collaborators at CalTech.

When I began spinal-cord research, I was most interested in neural connections and the complex circuitry they form. I decided that no biological system is better suited to ask questions of this nature than vision, specifically, the retina. To my great fortune, right there at UCLA was a world renowned photoreceptor physiologist, Dr. Gordon Fain, and his highly successful and brilliant disciple, Dr. Alapakkam “Sam” Sampath. I sought to join Dr. Sampath’s lab with success and I began my Ph.D. journey in the Spring of 2016.

The Sampath lab was an environment comprised of experienced students, post-doctoral researchers, and a wealth of collaborators across the globe, and I quickly became a part of the team. At the time I joined the lab, Sam had recently moved from the Keck School of Medicine (USC) to UCLA and, albeit functional for experiments, the lab was in the process of upgrading our physiology rigs and waiting for the Jules Stein Eye Institute to finish remodeling so the lab could move to its final location. I was able to use my hardware and software experience to upgrade the existing acquisition systems and to build new light stimulus pathways. In 2017, the lab moved to the Jules Stein building and I was fortunate enough to build my own rig.

Over my tenure in the Sampath lab, I developed novel methods for analyzing time-series, electrophysiological data. I contributed to mathematical modeling of photoreceptor light responses, where I leveraged the power of resampling statistics for model selection, uncertainty quantification and parameter estimation. I contributed to an open source software acquisition system and wrote a MATLAB-based application to visualize and analyze electrophysiological data offline. Aside from the technical work, I contributed to 8 collaborations, from which 4 separate NIH grants were awarded, 4 manuscripts were published (1 more in preparation as of Apr 20, 2023), and several conference proceedings were published (for example: Chung et al., 2022; Kim et al., 2018). Below, I’ve detailed my contributions to science.

Scientific Contributions (to date)

During my time in the laboratory of Patricia E. Phelps, I focused primarily on investigating the therapeutic potential of OECs in regenerating functional circuits following complete spinal cord injury. As a consequence of my technical background and my multiple roles within the lab, I was able to contribute to several projects with collaborators. During my tenure in the lab of Alapakkam Sampath, I was fortunate to leverage my technical background and my passion for math and statistics to contribute novel research and expand understanding of light detection and processing in the retina.

  1. A major contributing factor to any cellular transplant therapy is that of cell survival. By using intrinsic labeling in commercially available, eGFP transgenic Sprague Dawley rats, I assisted in generating OEC primary cultures that we transplanted into age-matched female Sprague Dawley rats which had received spinal cord injury. Using immunohistochemical and stereological methods, I quantified the amount of surviving control fibroblasts or OECs 1, 2, and 4 weeks post-injury and assessed the extent of serotonergic (5-HT) axon die back. I also organized and assisted in the surgical implantation of transcranial stimulation electrodes, electromyographic recording electrodes, and cellular implants. Using transcranial stimulation to evoke descending potentials and assess potential regenerated connectivity, I helped evaluate rats at 2 and 7 months after injury. We found that training, spinal cord stimulation, and OEC treatment yielded moderate functional recovery in spinal transected rats.
    • R. R. Khankan, K. G. Griffis, I. B. Wanner, H. Zhong, R. R. Roy, V. R. Edgerton, P. E. Phelps. Survival and migration of adult rat eGFP-OECs after a complete spinal cord transection. Program No. 466.02. 2013 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2013. Online.
    • A. K. Yeung, G. Garcia-Alias, K. G. Griffis, R. R. Khankan, H. Zhong, *R. R. Roy, P. E. Phelps, V. Edgerton. Spinal cord epidural stimulation and climb training enhance axon regeneration in rats transplanted with olfactory ensheathing cells after a complete spinal cord transection. Neuroscience 2015 Abstracts. Chicago, IL: Society for Neuroscience, 2015. Online.
  2. Following the cell viability experiments, I hypothesized that transplanted OECs affected glial scar formation in a potentially beneficial way. Using immunohistochemistry and confocal microscopy, I evaluated astrocyte morphology around the lesion, as well as the presence of activated microglia and invading macrophages. We showed that, compared to control fibroblast treated rats, the acute immune response and the deposition of CS-56+ proteins were markedly reduced in OEC treated rats at all acute time points following injury. We determined that OECs reduce lesion size in early acute responses, but by 8 weeks these effects, along with the OECs, are diminished. Further, 5-HT+ axons were more abundant in OEC treated rats, implying that OECs modulate the immune response to facilitate axonal regeneration. The evolution of this project produced two abstracts and two manuscripts in 2016 and 2018.
    • Thornton, M. A., Mehta, M. D., Morad, T. T., Ingraham, K. L., Khankan, R. R., Griffis, K. G., Yeung, A. K., Zhong, H., Roy, R. R., Edgerton, V. R., & Phelps, P. E. (2018). Evidence of axon connectivity across a spinal cord transection in rats treated with epidural stimulation and motor training combined with olfactory ensheathing cell transplantation. Experimental Neurology, 309, 119–133. https://doi.org/10.1016/J.EXPNEUROL.2018.07.015
    • Khankan, R. R., Griffis, K. G., Haggerty-Skeans, J. R., Zhong, H., Roy, R. R., Reggie Edgerton, V., & Phelps, P. E. (2016). Olfactory ensheathing cell transplantation after a complete spinal cord transection mediates neuroprotective and immunomodulatory mechanisms to facilitate regeneration. Journal of Neuroscience, 36(23). https://doi.org/10.1523/JNEUROSCI.0085-16.2016
    • Khankan, R.R., Ingraham, K.L., Haggerty-Skeans, J.R., Griffis, K.G., Zhong, H., Roy,R., Edgerton, V.R., Phelps, P.E. Olfactory ensheathing cells reduce inhibitory factors at the astroglial scar-border after a complete mid-thoracic spinal cord transection. Program No. 338.07/V24 Neuroscience 2015 Abstracts. Chicago, IL: Society for Neuroscience, 2015. Online.
    • R. R. Khankan, K. G. Griffis, D. N. Perez, J. R. Haggerty-Skeans, H. Zhong, R. R. Roy, V. R. Edgerton, *P. E. Phelps. Olfactory ensheathing cells and fibroblasts differ their modification of the lesion site after complete spinal cord transection. Program No. 422.26. 2014 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2014. Online.
  3. I became interested in cellular physiology and had the opportunity to use both my cell-culture experience and statistical knowledge to assist a colleague in studying the role of calcium oscillations in a module of acute lung injury of human pulmonary artery smooth muscle cells (hPASMCs). To study possible mechanisms, we investigated effects of IL-1b on calcium flux in hPASMCs in response to vasoconstrictor endothelin-1. I developed an analysis method, using machine learning and other statistical methods, to identify oscillating and non-oscillating responders. We showed that IL-1b is strongly associated with increases in oscillating responders. Follow-up work from this project is ongoing, and a manuscript is in preparation.
    • Elizabeth H. Kim, Khris G. Griffis, Meredith Sheppard, Suliman Alamro, Daniel Tabari, Alan Garfinkel, and Heather D. Jones. Calcium Oscillations in Human Pulmonary Artery Smooth Muscle Cells: Developing a Hierarchical Clustering Method for Analysis and the Effects of IL-1b. The FASEB Journal 2018 32:1_supplement, 628.1-628.1
  4. In a collaboration between the laboratories of Alapakkam Sampath and Anthony J. Aldave, I did whole-cell patch recordings on isolated mouse corneal endothelial cells in culture to study the functional role of SLC4A11 in a murine model of congenital hereditary endothelial dystrophy (CHED). SCL4A11 is essential for facilitating energy producing glutaminolysis, maintaining antioxidant signaling, and preventing apoptosis in corneal endothelial cells. We showed that reduced steady-state ATP levels and subsequent activation of the AMPK-p53 pathway provide a link between the metabolic functional deficit and transcriptome alterations. We also found evidence that insufficient ATP to maintain the Na+/K+-ATPase corneal endothelial pump is the cause of the edema that characterizes SLC4A11-associated corneal endothelial dystrophies.
    • Zhang, W., Frausto, R., Chung, D.D., Griffis, C.G., Kao, L., Chen, A., Azimov, R., Sampath, A.P., Kurtz, I., Aldave, A.J. (2020) Energy shortage in human and mouse models of SLC4A11-associated corneal endothelial dystrophies . Investigative Ophthalmology & Visual Science, 61(8), 39.
    • Chung, D., Chen, A., Choo, C., Zhang, W., Griffis, C., Bonezzi, P., Sampath, A.P., Aldave, A.J. (2022) Investigation of the functional impact of CHED- and FECD4-associated SLC4A11 mutations in human corneal endothelial cells . Investigative Ophthalmology & Visual Science, 63(7), 3624-A0189.
  5. I provided patch-clamp recordings from rod photoreceptors and statistical analysis to a model of mouse cone photoreceptors developed by Jürgen Reingruber and Gordon Fain. I helped to show that the kinetic changes that transform the rod response into that of the cone are characterized by these three key parameters: 1) reduction in transduction amplification, 2) increased dark turnover rate of cGMP, and 3) increased decay rate of activated phosphodiesterase.
    • Reingruber, J., N.T. Ingram, Griffis, K.G., and G.L. Fain. 2020. A kinetic analysis of mouse rod and cone photoreceptor responses. Journal of Physiology, in press.
  6. Extending from the collaboration in which I used information theoretic clustering of calcium oscillations in hPASMCs, I collaborated with Alan Garfinkel and Christopher Colwell to study oscillations in the core body temperature (CBT) of mice with a genetic perturbation (Q175) that mimics Huntington’s disease (HD) in humans. Circadian rhythms in CBT have been widely studied, but fewer studies have explored higher-frequency (ultradian) rhythms in detail. We analyzed CBT recordings from young and middle-aged wild-type mice as well as from the Q175 model of HD, at sufficient temporal resolution to address the question of ultradian rhythms. We used model selection methods to show that the overall circadian pattern was better fit by a square wave than a sine wave. Then, using Fourier analysis of the CBT rhythms, we identified the spectral signature of an 8-hour oscillation that occurs in the night but not the day, an observation that can be confirmed by direct inspection of the rhythms. This diurnal amplitude modulation of the 8-hour rhythm was lost with aging as well as in the HD model. Thus, the impact of aging and disease is seen here in the loss of the ability to separate rhythms into a daytime phase and a nighttime phase. These findings raise the possibility that ultradian rhythms in CBT may be a useful biomarker for the pathology within the central nervous system.
    • Griffis, C.G., Mistry, J., Islam, K., Cutler, T., Colwell, C.S., & Garfinkel, A. (2022) Circadian and ultradian rhythms in normal mice and in a mouse model of Huntington’s disease. Chronobiology International, 39, 513–524.
  7. Light adaptation adjusts the sensitivity of vision as ambient illumination changes. Adaptation for scotopic (rod) vision is known to occur partly in the rods and partly in the rest of the retina from presynaptic and postsynaptic mechanisms. We recorded light responses of rods and rod bipolar cells to identify different components of adaptation and study their mechanisms. We show that bipolar-cell sensitivity largely follows adaptation of the rods, but that light too dim to adapt the rods produces a linearization of the bipolar-cell response dynamics and a surprising decrease in maximum response amplitude, both mediated by a change in intracellular Ca2+. These findings provide a new understanding of how the retina responds to changes in ambient illumination.
    • Khris G. Griffis, Katherine E. Fehlhaber, Fred Rieke, and Alapakkam P. Sampath. (2023). Light adaptation of retinal rod bipolar cells. Submitted to J. Neurosci., pending acceptance.
    • Griffis, C., Sampath, A.P.. (2021) Rod bipolar cell contributions to changes in response sensitivity during light adaptation . Investigative Ophthalmology & Visual Science, 62(8), 2004.
  8. In collaboration with Johan Pahlberg, Ph.D. (NIH/NIDCR), I dissected contributions of transduction-cascade proteins to the continuous noise that obscures the single-photon response in rod photoreceptors and pinpointed the molecular origin of discrete noise, which is indistinguishable from the single-photon response, albeit in the absence of light. To do so, we used novel murine models with graded reductions of G-alpha transducin-1 and PDE-6 levels, and made whole-cell patch recordings in individual rods. Through my experiments, I characterized rod continuous noise and investigated its molecular origin to ask if any one component both sets the continuous noise level and limits the detection of single photons.
    • Christopher G. Griffis*, Ulisse Bocchero*, Alapakkam P. Sampath and Johan Pahlberg. Origins of discrete and continuous dark noise in rod photoreceptors. In preparation.

1: I was that kid in high school who hacked the brand new windows 98 classroom so the teacher couldn't see I was playing solitaire instead of practicing typing.

References

  • Chung, D., Chen, A., Choo, C., Zhang, W., Griffis, C., Bonezzi, P., Sampath, A.P., & Aldave, A.J. (2022) Investigation of the functional impact of CHED-and FECD4-associated SLC4A11 mutations in human corneal endothelial cells. In Investigative Ophthalmology & Visual Science. The Association for Research in Vision and Ophthalmology, pp. 3624–A0189.
  • Einstein, A. (1930) What I Believe: Living Philosophies XIII. Forum and Century, LXXXIV, 192.
  • Griffis, C.G. (2022) Mechanisms of Detection Sensitivity and Adaptation in the Rod Visual Pathway (PhD thesis).
  • Kim, E.H., Griffis, K.G., Sheppard, M., Alamro, S., Tabari, D., Garfinkel, A., & Jones, H.D. (2018) Calcium Oscillations in Human Pulmonary Artery Smooth Muscle Cells: Developing a Hierarchical Clustering Method for Analysis and the Effects of IL-1b. In The FASEB Journal. Wiley Online Library, pp. 628–621.
by:
Khris Griffis
https://khrisgriffis.com
Neurophysiology | Statistics | Biosignals Analysis | Data Science