Congratulations to the winners of the first-ever ICTR Team Science Award!
Outcomes After Critical Illness and Surgery- Mental Health Group
Prostate Cancer Research Team
The “Targeted Nanomedicine team” was born out of an initial collaboration between the Dr. Sujatha Kannan and Dr. Kannan Rangaramanujam labs to begin to address the largely unmet need for pharmacological interventions for perinatal brain injury. It has now expanded to involve several labs across campus. Currently, therapeutic avenues are limited, resulting in high rates of cerebral palsy after perinatal insult. Through this initial collaboration, nanoparticle-drug conjugates were developed to target drug delivery to microglia and remediate microglial-driven inflammatory cascades responsible for injury in many neurological conditions characterized by neuroinflammation. To do this, the team conjugates their drug of interest to hydroxyl-terminated poly(amidoamine) dendrimers. Utilizing this approach, they have been able to take previously poor drug candidates for the brain and make them effective by improving brain penetration and bioavailability. Currently, the team is conducting interdisciplinary IND-enabling preclinical work via a milestone-driven U01 grant. This project combines expertise in drug discovery, chemical engineering, and preclinical disease modeling to:
- Optimize the drug-conjugate itself.
- Develop and conduct pharmacokinetic and pharmacodynamics assessments.
- Conduct dose-finding preclinical work in a large animal model of neonatal neuroinflammation.
Outcomes After Critical Illness and Surgery—Mental Health Group
The interdisciplinary Mental Health team within the Outcomes After Critical Illness and Surgery (OACIS) research group came together to study delirium during critical illness and long-term mental health outcomes in survivors of critical illness. Their pioneering collaborative work led to the discovery that up to 80% of patients who survive critical illness live with new or worsened mental health and cognitive outcomes, contributing to the term Post-Intensive Care Syndrome. Since this important discovery, additional team members were added to continue advancing ways to understand and improve mental health outcomes in survivors of critical illness and their families. Specifically, the scientific goals of this multi-disciplinary team are to:
- Understand long-term mental health and cognitive outcomes of critical care survivors
- Improve awareness among patients, families, and clinicians about post-intensive care syndrome – including negative mental health impacts.
- Promote best practices in the ICU to help protect patient’s mental health and cognitive function.
- Design and test evidence-based interventions to improve patient outcomes.
Role on Team
|Kannan Rangaramanujam, PhD||Johns Hopkins School of Medicine, Ophthalmology||Principal Investigator|
|Sujatha Kannan, MD||Johns Hopkins School of Medicine, Anesthesiology and Critical Care Medicine||Principal Investigator|
|Barbara Slusher, PhD||Johns Hopkins School of Medicine, Neurology/Johns Hopkins Drug Discovery||Co-Investigator|
|Frances Northington, MD||Johns Hopkins School of Medicine, Pediatrics||Co-Investigator|
|Nirnath Sah, PhD||Johns Hopkins School of Medicine, Anesthesiology and Critical Care Medicine||Postdoctoral Fellow|
|Jinhuan Liu, BSN||Johns Hopkins School of Medicine, Anesthesiology and Critical Care Medicine||Lab Manager|
|Amanda Fowler, BS||Johns Hopkins School of Medicine, Anesthesiology and Critical Care Medicine||Lab Technician|
|Alicia Chime, BS||Johns Hopkins School of Medicine, Anesthesiology and Critical Care Medicine||Lab Technician|
|Anjali Sharma, PhD||Johns Hopkins School of Medicine, Ophthalmology||Research Associate|
|Wathsala Liyanage, PhD||Johns Hopkins School of Medicine, Ophthalmology||Postdoctoral Fellow|
|Elizabeth Khoury, PhD||Johns Hopkins School of Medicine, Anesthesiology and Critical Care Medicine||Research Associate|
|Tony Wu, BS||Johns Hopkins WSE: Chemical and Biomolecular Engineering||Graduate Student|
|Rana Rais, PhD||Johns Hopkins School of Medicine, Neurology||Co-Investigator|
|Jesse Alt, PhD||Johns Hopkins School of Medicine, Johns Hopkins Drug Discovery||Staff Scientist|
|Debbie Flock, BS||Johns Hopkins School of Medicine, Pediatrics||Lab Manager|
|Victoria Turnbill, BS||Johns Hopkins School of Medicine, Pediatrics||Lab Technician|
Check out some of the work that the Targeted Nanomedicine team is most proud of:
- Kannan S, Dai H, Navath RS, Balakrishnan B, Jyoti A, Janisse J, Romero R, Kannan RM. Dendrimer-based postnatal therapy for neuroinflammation and cerebral palsy in a rabbit model. Sci Transl Med. 2012 Apr 18;4(130):130ra46. doi: 10.1126/scitranslmed.3003162. PMID: 22517883; PMCID: PMC3492056.
- Nance E, Kambhampati SP, Smith ES, Zhang Z, Zhang F, Singh S, Johnston MV, Kannan RM, Blue ME, Kannan S. Dendrimer-mediated delivery of N-acetyl cysteine to microglia in a mouse model of Rett syndrome. J Neuroinflammation. 2017 Dec 19;14(1):252. doi: 10.1186/s12974-017-1004-5. Erratum in: J Neuroinflammation. 2018 Jan 12;15(1):14. PMID: 29258545; PMCID: PMC5735803.
- Turk BR, Nemeth CL, Marx JS, Tiffany C, Jones R, Theisen B, Kambhampati S, Ramireddy R, Singh S, Rosen M, Kaufman ML, Murray CF, Watkins PA, Kannan S, Kannan R, Fatemi A. Dendrimer-N-acetyl-L-cysteine modulates monophagocytic response in adrenoleukodystrophy. Ann Neurol. 2018 Sep;84(3):452-462. doi: 10.1002/ana.25303. PMID: 30069915; PMCID: PMC6454885.
Prostate Cancer Research Team
Their molecular-patho-epidemiology team came together because mentors recognized their mutual interest in intraprostatic inflammation in the etiology and progression of prostate cancer—from the pathology perspective and from the epidemiology perspective—and introduced them. (Mentorship and endorsement matters!!!) From this initial team in 1999, they have expanded to include cancer biologists, geneticists, and clinicians from multiple clinical specialties, plus students and fellows. Among other achievements, their team conducted the first prospective (temporally correct) study showing that intraprostatic inflammation is associated with an increased risk of prostate cancer in men without an indication for biopsy. The team’s current goals continue to be to identify molecular indicators of prostate cancer risk and progression to lethality, especially molecular factors that may explain the profound racial disparity and to develop those markers for use in prevention, predicting prognosis, and guiding intervention.
Role on Team
|Elizabeth Platz, ScD||Johns Hopkins Bloomberg School of Public Health, Epidemiology||PI/Co-PI/Co-I|
|Angelo De Marzo, MD, PhD||Johns Hopkins School of Medicine, Pathology||PI/Co-PI/Co-I|
|Alan Meeker, PhD||Johns Hopkins School of Medicine, Pathology||PI/Co-PI/Co-I|
|William Nelson, MD, PhD||Johns Hopkins School of Medicine, Oncology||PI/Co-PI/Co-I|
|Srinivasan Yegnasubramanian, MD, PhD||Johns Hopkins School of Medicine, Oncology||PI/Co-PI/Co-I|
|Corinne Joshu, PhD||Johns Hopkins Bloomberg School of Public Health, Epidemiology||PI/Co-PI/Co-I|
|Shawn Lupold, PhD||Johns Hopkins School of Medicine, Urology||PI/Co-PI/Co-I|
|Jiayun Lu, PhD||Johns Hopkins Bloomberg School of Public Health, Epidemiology||Biostatistician|
Check out some of the work that the Prostate Cancer Research Team is most proud of:
- Platz EA, Kulac I, Barber JR, Drake CG, Joshu CE, Nelson WG, Lucia MS, Klein EA, Lippman SM, Parnes HL, Thompson IM, Goodman PJ, Tangen CM, De Marzo AM. A Prospective Study of Chronic Inflammation in Benign Prostate Tissue and Risk of Prostate Cancer: Linked PCPT and SELECT Cohorts. Cancer Epidemiol Biomarkers Prev. 2017 Oct;26(10):1549-1557. doi: 10.1158/1055-9965.EPI-17-0503. Epub 2017 Jul 28. PMID: 28754796; PMCID: PMC5626618.
- Heaphy CM, Yoon GS, Peskoe SB, Joshu CE, Lee TK, Giovannucci E, Mucci LA, Kenfield SA, Stampfer MJ, Hicks JL, De Marzo AM, Platz EA, Meeker AK. Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for metastasis and death. Cancer Discov. 2013 Oct;3(10):1130-41. doi: 10.1158/2159-8290.CD-13-0135. Epub 2013 Jun 18. PMID: 23779129; PMCID: PMC3797255.
- Marrone MT, Joshu CE, Peskoe SB, De Marzo AM, Heaphy CM, Lupold SE, Meeker AK, Platz EA. Adding the Team into T1 Translational Research: A Case Study of Multidisciplinary Team Science in the Evaluation of Biomarkers of Prostate Cancer Risk and Prognosis. Clin Chem. 2019 Jan;65(1):189-198. doi: 10.1373/clinchem.2018.293365. Epub 2018 Dec 5. PMID: 30518666; PMCID: PMC7375195.
Neural Port Project* (Promising New Team)
Their research project originated from the collaboration of a reconstructive surgery student and a biomedical engineering PhD student with a shared interest in designing implantable electrodes to monitor neural activity in January 2020. Both parties initially expressed interest in improving the lives of amputees and individuals suffering from limb loss and its aftereffects (including loss of sensation, phantom limb pain, etc.). They decided that approaching the problem from both the clinical and engineering perspective would not only be most efficient, but it would also be more inclusive of a variety of scientific perspectives and ideas. As a whole, their team aims to bridge the gap between what happens in the lab and what happens in the operating room. The team is currently investigating a unique reconstructive surgery that could potentially lead to improved signal amplification for prosthesis control in amputees and to reduced neuropathic pain in amputees and others suffering from nerve damage. They are also currently investigating how surgical reconstruction (drastic changes in tissue) can lead to changes in the signal acquisition post-regeneration for interfacing humans with robotic prostheses.
Role on Team
|Alexis Lowe, PhD candidate||Johns Hopkins School of Medicine, Biomedical Engineering||Team Lead (exploratory research)|
|Connor Glass, MD candidate||Johns Hopkins School of Medicine, Plastic Surgery||Team Lead (translational research)|
|Ana Rosu, BS candidate||Johns Hopkins Whiting School of Engineering, Biomedical Engineering||Research Assistant (animal signal acquisition)|
|Alyssa Lee, BS candidate||Johns Hopkins Krieger School of Arts and Sciences, Molecular and Cellular Biology||Research Assistant (animal tissue processing/analysis)|
|Jacky Tian, MS candidate||Johns Hopkins School of Medicine, Biomedical Engineering||Co-investigator (electrode design and development)|
|Shipeng Wang, MS candidate||Johns Hopkins School of Medicine, Biomedical Engineering||Co-investigator (tissue imaging)|
|Martin Prados, BS candidate||Johns Hopkins Whiting School of Engineering, Biomedical Engineering||Research Assistant (electrode design and development)|
|Sami Tuffaha, MD||Johns Hopkins School of Medicine, Plastic Surgery||Co-principal Investigator|
|Nitish Thakor, PhD||Johns Hopkins School of Medicine, Biomedical Engineering||Co-principal Investigator|
Check out some of the work that the Neural Port Project is most proud of:
- Poster presentation at ASPN Nerve Week (Jan 2021) TITLE: Vascularized Denervated Muscle Targets Deliver High Quality Signal Amplification AUTHORS: Nicholas von Guionneau, Connor Glass, Alexis Lowe, Alison Wong, Thomas G.W. Harris, Nitish V. Thakor, Sami Tuffaha
- Review Paper published in Bioelectronic Medicine (Feb 2021) TITLE: Cut Wires: the electrophysiology of regenerated tissues AUTHORS: Alexis Lowe, Nitish V. Thakor
- Conference Paper published at IEEE Neural Engineering (Apr 2021) TITLE: Laser Speckle Contrast Imaging Insufficiently Sensitive to Detect Changes in Muscle Blood Flow During Electrical Stimulation AUTHORS: Alexis Lowe, Maria Rivera-Santana, Kiara Quinn, Yucheng Tian, Alyssa Lee, Nitish Thakor