UCLA CTSI K Workshop - July 28, 2022 Considerations in Applying for a K99 Award: the NIH "Pathway to Independence" presented by Dr. Christopher Evans, PhD

1. K99/R00 - Awards
“Pathway to Independence”
Chris Evans
310 206 7884
cevans@ucla.edu
1-2 years of
Mentored
Research
3 years of
Independent
Research
+

2. https://www.niaid.nih.gov/grants-contracts/choose-award-career-stage
https://researchtraining.nih.gov/programs/career-development
K-Kiosk for Comparisons

3. PURPOSE:
K99 - To support Career/Research Transition to a faculty position and provides 1-2 years of mentored
support for, advanced (but not too advanced) postdoctoral research scientists.
R00 - To support the second phase of a Career/Research Transition award and provides 1 -3 years of
independent research support (R00) contingent on securing an independent research position. Award
recipients will hopefully compete successfully for independent R01 support from the NIH during the R00
research transition award period.
Bottom Line
2 years mentored research – move to faculty slot – 3 years R01-like funding
Questions and Answers
https://grants.nih.gov/grants/new_investigators/QsandAs.htm
Blog spot
http://k99advice.blogspot.com
“There’s a lively exchange occurring among scientists on Twitter right now regarding the advice that you need a Cell, Nature, or Science
(CNS) paper in order to land a faculty job.”

4. REQUIREMENTS ELIGIBILITY FOR APPLICATION:
 K99 will support non-US citizens but one must be in the US for both training and R00.
 Must be at the time of application submission (or resubmission) in postdoctoral training.
Evidence for independence, and therefore lack of eligibility, includes: The candidate has a
full-time faculty position. The candidate received a start-up package for support of his/her
independent research.
 Must have a terminal clinical or research doctorate (including Ph.D., M.D., D. O., D.C., N.D.,
D.D.S., D.V.M., Sc.D., D.N.S., Pharm. D.,) or equivalent doctoral degree, or a combined
degree.
 no more than 4 years of postdoctoral research experience since completing the
requirements of the doctoral degree in or outside USA (resubmissions must also comply
with this requirement). This time can be extended due to pregnancy, parenting, military
service and other personal issues reducing ability to work. Clinical training time with no
research involvement (e.g., residency training) is not counted against the 4-year limit.

5. Further Continuation of Temporary Extension of Eligibility for the NIH K99/R00 Pathway to Independence Award During
the COVID-19 Pandemic
Release Date: February 4, 2022
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-22-062.html
Under normal circumstances, individuals must have no more than four years (i.e., 48 months) of postdoctoral research
experience to be eligible to apply for a K99/R00 Pathway to Independence award. NIH will be providing the following
extensions in eligibility for prospective candidates:
Individuals whose final due date for eligibility based on a 48-month eligibility window is February/March 2022 will be
granted a two-receipt cycle extension (roughly eight additional months).
Individuals whose final due date for eligibility based on a 48-month eligibility window is June/July 2022 will be granted a
one-receipt cycle extension (roughly four additional months).
Individuals who have previously received the two-cycle automatic COVID-based eligibility extension for K99 submission are
not eligible for an additional extension.
Implementation
The two-receipt cycle extension in eligibility under this Notice applies only to applicants for a K99/R00 award under one of
the parent Funding Opportunity Announcements (PA-20-187, PA-20-188, and PA-20-189).
For eligible applicants submitting new or resubmission applications, the two-receipt cycle extension will be automatically
accepted by the NIH; no additional documentation is required. However, prospective K99 applicants who wish to receive
non-COVID-related extensions (such as those for childbirth, adoption, family, etc.) must continue to provide relevant
documentation.

6. REQUIREMENTS/ELIGIBILITY FOR R00:
The second (R00) phase provides up to 3 years of independent research support, which is
contingent on satisfactory progress during the K99 phase and an approved, independent,
tenure-track (or equivalent) faculty position.
R00 awards will generally only be made to those K99 PIs who accept independent, tenure-
track (or equivalent) faculty positions in the USA by the end of the K99 award period.
Note: You can’t take your R00 outside of the country (even Canada or Mexico).
NIH can get sticky giving R00 awards for faculty staying in the same institution and with
questionable job titles… getting an independent job is now tough and job seeking needs to
occur soon after receiving the award….
Check with an NIH institute project officer and try to meet at a conference or via zoom!

7. National Cancer Institute (NCI)
National Eye Institute (NEI)
National Heart, Lung, and Blood Institute (NHLBI)
National Human Genome Research Institute (NHGRI)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
National Center for Complementary and Integrative Health (NCCIH)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Drug Abuse (NIDA)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute of Environmental Health Sciences (NIEHS)
National Institute of General Medical Sciences (NIGMS)
National Institute of Mental Health (NIMH)
National Institute of Neurological Disorders and Stroke (NINDS)
National Institute of Nursing Research (NINR)
National Library of Medicine (NLM)
Division of Program Coordination, Planning and Strategic Initiatives, Office of Research Infrastructure Programs (ORIP)
National Institute on Minority Health and Health Disparities (NIMHD)
Special Note: Not all NIH Institutes and Centers participate in Parent Announcements ( for example NINDS does not participate in Clinical Trials).
(CRITCAL – TALK TO PROGRAM STAFF!)
PARTICIPATING INSTITUTES:

9. Make yourself known to a PO and ask advice in the
institute you are applying to!
https://researchtraining.nih.gov/programs/career-development/K99-R00
NIH Funding Opportunity Announcements
The links below provide details on funding amounts period of performance, application
dates and eligibility:
NIH Pathway to Independence Award (Parent K99/​R00 - Clinical Trial Required)
https://grants.nih.gov/grants/guide/pa-files/PA-18-397.html
NIH Pathway to Independence Award (Parent K99/​R00 - Independent Clinical Trial Not
Allowed)
https://grants.nih.gov/grants/guide/pa-files/PA-18-398.html

10. What reviewers will look for?
1) Your CV: Good track record – high impact publications –and publications that have primary authorship – add a link
to all your publications. Explain contributions to “team science” multi-author publications. Highlight success in
different environments, advise to highlight objectives of training in personal statement.
2) Preliminary data: innovation, potential impact, rigor of the research project to the NIH institute you are applying to.
This is a training grant and needs to demonstrate good rationale for acquiring new techniques, rigor of
methodologies and creating a base for accomplishing the desired project and transitioning to the ROO phase. Avoid
acronyms explain the importance of the problem and your hypothesis rigorously – get reviewers excited but don’t
oversell and accurately relay impact – remember reviews are unlikely to be your field expertts.
3) Training plan: can be more/just as important than the research ideas. This is a place in which reviewers can get very
picky, especially if they are not swayed by the science. Staying in one location and area of research for all training is
considered a negative – complementary approaches to fulfill your career goals positive. Transitioning to a totally
new field without continuity with past research a difficult sell.
4) Reference letters: obtain from well-established and high-impact researchers in the field. Don’t go to your friends
down the hall – cultivate letters from faculty that are relevant in your area and ask your mentor to help you out.
Compliment weaknesses in your primary mentors CV in areas of research, mentorship and technical expertise.
5) Mentor/training environment is critical. Positives are NIH grants for mentor, training track record (use co-mentor if
any weaknesses), institutional opportunities/cores/seminars/courses etc, different from Ph.D. mentor/environment,
the K99 component has synergism with prior career scientific trajectory.

12. Different for applications with CT

13. Rigor and Authentication of Reagents:
- Remember sex /gender needs to be addressed
- Ask statisticians at UCLA such as David Elashoff for advice – power analysis etc
- Reagents need to be verified – using an antibody to XXX doesn’t cut it
https://ctsi.ucla.edu/funding/files/view/docs/RigorandReproducibility_Rochester.pdf
https://grants.nih.gov/reproducibility/module_1/presentation.html

14. Case Histories
Note: CTSI have uploader successful applications. Chat with a successful K99 trainee.

15. 1: Bredy TW, Barad M. Social modulation of associative fear learning by pheromone communication. Learn Mem.
2008 Dec 30;16(1):12-8. doi:10.1101/lm.1226009. Print 2009 Jan. PubMed PMID: 19117912; PubMed Central
PMCID: PMC2632855.
2: Bredy TW, Barad M. The histone deacetylase inhibitor valproic acid enhances acquisition, extinction, and
reconsolidation of conditioned fear. Learn Mem. 2008Jan 3;15(1):39-45. doi: 10.1101/lm.801108. Print 2008 Jan.
PubMed PMID: 18174372;PubMed Central PMCID: PMC2170514.
3: Bredy TW, Wu H, Crego C, Zellhoefer J, Sun YE, Barad M. Histone modifications around individual BDNF gene
promoters in prefrontal cortex are associated with extinction of conditioned fear. Learn Mem. 2007 Apr
6;14(4):268-76. Print 2007Apr. PubMed PMID: 17522015; PubMed Central PMCID: PMC2216532.
4: Bredy TW, Brown RE, Meaney MJ. Effect of resource availability on biparental care, and offspring neural and
behavioral development in the California mouse (Peromyscus californicus). Eur J Neurosci. 2007 Jan;25(2):567-75.
PubMed PMID:17284199.
5: Bredy TW. Behavioural epigenetics and psychiatric disorders. Med Hypotheses. 2007;68(2):453. Epub 2006 Sep
11. PubMed PMID: 16963190.
6: Zhang TY, Bagot R, Parent C, Nesbitt C, Bredy TW, Caldji C, Fish E, AnismanH, Szyf M, Meaney MJ. Maternal
programming of defensive responses through ustained effects on gene expression. Biol Psychol. 2006 Jul;73(1):72-
89. Epub2006 Feb 28. Review. PubMed PMID: 16513241.
7: Bredy TW, Zhang TY, Grant RJ, Diorio J, Meaney MJ. Peripubertal environmental enrichment reverses the effects
of maternal care on hippocampal development and glutamate receptor subunit expression. Eur J Neurosci. 2004
Sep;20(5):1355-62.PubMed PMID: 15341607.
8: Bredy TW, Lee AW, Meaney MJ, Brown RE. Effect of neonatal handling and paternal care on offspring cognitive
development in the monogamous Californiamouse (Peromyscus californicus). Horm Behav. 2004 Jun;46(1):30-8.
PubMed PMID:15215039.
9: Bredy TW, Grant RJ, Champagne DL, Meaney MJ. Maternal care influences neuronal survival in the hippocampus
of the rat. Eur J Neurosci. 2003Nov;18(10):2903-9. PubMed PMID: 14656341.
10: Bredy TW, Humpartzoomian RA, Cain DP, Meaney MJ. Partial reversal of the effect of maternal care on cognitive
function through environmental enrichment. Neuroscience. 2003;118(2):571-6. PubMed PMID: 12699791.
Good pedigree, most first authored papers, consistent productivity (medium-good
impact), not NIDA obvious, but NIDA interested in learning and memory
processes/plasticity, different labs PhD and postdoc.
TIMOTHY W. BREDY
Associate Professor,
The University of
Queensland, Brisbane,
Australia
Ph.D., McGill
University Then Postdoc
at UCLA. R00 - UCI

16. Kate Wassum Ph. D.,
Professor Psychology, UCLA
PhD/Postdoc UCLA
Primary : Learning and
Behavior
Secondary: Behavioral
Neuroscience
1: Wassum KM, Ostlund SB, Balleine BW, Maidment NT. Differential dependence o fPavlovian incentive
motivation and instrumental incentive learning processes on dopamine signaling. Learn Mem. 2011 Jun
21;18(7):475-83.
2: Wassum KM, Cely IC, Balleine BW, Maidment NT. Micro-opioid receptor activation in the basolateral
amygdala mediates the learning of increases but not decreases in the incentive value of a food reward. J
Neurosci. 2011 Feb 2;31(5):1591-9.
3: Ostlund SB, Wassum KM, Murphy NP, Balleine BW, Maidment NT. Extracellular dopamine levels in
striatal subregions track shifts in motivation and response cost during instrumental conditioning. J Neurosci.
2011 Jan 5;31(1):200-7.
4: Wassum KM, Cely IC, Maidment NT, Balleine BW. Disruption of endogenous opioid activity during
instrumental learning enhances habit acquisition. Neuroscience.2009 Oct 20;163(3):770-80. doi:
10.1016/j.neuroscience.2009.06.071. Epub 2009 Jul18. PubMed PMID: 19619616; PubMed Central PMCID:
PMC3065789.
5: Wassum KM, Ostlund SB, Maidment NT, Balleine BW. Distinct opioid circuits determine the palatability
and the desirability of rewarding events. Proc NatlAcad Sci U S A. 2009 Jul 28;106(30):12512-7. doi:
10.1073/pnas.0905874106. Epub2009 Jul 13. PubMed PMID: 19597155; PubMed Central PMCID:
PMC2718390.
6: Wassum KM, Evans CJ. International Narcotics Research Conference - 39thAnnual Meeting. IDrugs. 2008
Sep;11(9):646-9. PubMed PMID: 18763214.
7: Wassum KM, Tolosa VM, Wang J, Walker E, Monbouquette HG, Maidment NT. SiliconWafer-Based
Platinum Microelectrode Array Biosensor for Near Real-Time Measurement of Glutamate in Vivo. Sensors
(Basel). 2008;8(8):5023-5036. PubMedPMID: 19543440; PubMed Central PMCID: PMC2699285.
8: Wightman RM, Heien ML, Wassum KM, Sombers LA, Aragona BJ, Khan AS, AriansenJL, Cheer JF, Phillips
PE, Carelli RM. Dopamine release is heterogeneous within microenvironments of the rat nucleus
accumbens. Eur J Neurosci. 2007Oct;26(7):2046-54. Epub 2007 Sep 14. PubMed PMID: 17868375.
9: Cheer JF, Wassum KM, Sombers LA, Heien ML, Ariansen JL, Aragona BJ, Phillips PE, Wightman RM. Phasic
dopamine release evoked by abused substances requires cannabinoid receptor activation. J Neurosci. 2007
Jan 24;27(4):791-5. PubMedPMID: 17251418.
10: Cheer JF, Wassum KM, Wightman RM. Cannabinoid modulation of electrically evoked pH and oxygen
transients in the nucleus accumbens of awake rats. JNeurochem. 2006 May;97(4):1145-54. PubMed PMID:
16686693.
11: Heien ML, Khan AS, Ariansen JL, Cheer JF, Phillips PE, Wassum KM, WightmanRM. Real-time
measurement of dopamine fluctuations after cocaine in the brain of behaving rats. Proc Natl Acad Sci U S A.
2005 Jul 19;102(29):10023-8. Epub 2005Jul 8. PubMed PMID: 16006505; PubMed Central PMCID:
PMC1177422.
12: Cheer JF, Wassum KM, Heien ML, Phillips PE, Wightman RM. Cannabinoids enhance subsecond
dopamine release in the nucleus accumbens of awake rats. J Neurosci.2004 May 5;24(18):4393-400.
PubMed PMID: 15128853.
Good pedigree, many 1st
authored papers, consistent
productivity (high impact),
NIDA-related research. CV
exceptionally strong, many
awards……?????? No K99

17. I got a score 38 on my K99,
Here is the text from her summary statement that she allowed me to share:
Enthusiasm is tempered by the fact that the proposal is not really distinguished from the candidate’s
previous work in this environment. The training does not really appear to add to the applicant’s already
extensive abilities and experiences gained in this same environment with the same
mentors. ………………………….The case for additional training in these disciplines was difficult to
discern. Although the principal investigator has taken advantage of the thriving scientific resources at
UCLA during her graduate and postdoctoral training, the application was unclear how further training in
the same environment would achieve the goals of the K99. For example, the proposed K99 mentor, Dr
Maidment, is co-author on all the applicant’s publications from her time at UCLA, including the
predoctoral tenure. Similarly, the predoctoral mentor, Dr Balleine, continues as co-author on papers
described in the application as postdoctoral projects. …………………………….Drug studies will occur in the
independent phase so no obvious training in neuropharmacology will occur under this plan. Do not see
that the extra training proposed advances the applicant’s career prospects. The applicant already has
publications/work on methods proposed, i.e. use of Glu biosensors. The applicant also appears to have
extensive behavioral training. Does not seem appropriate for a K99 – the application seems to be
continuation of training rather than seeking really new opportunities. Continuing in same environment –
proposed mentor has been an important part of all her graduate and postdoc work to date and is senior
author on many of her publications.

18. Amynah Pradhan PhD
Canadian Citizen
PhD CNRS France,
Postdoc UCLA
Assistant Professor
Department of Psychiatry
University of Illinois
Good Pedigree, most 1st
authored papers, impact is
med (2010 high), NIDA
relevance – pain (opioids) – 6
years out of post-doc
motherhood (rules changed
from 5 to 4 years after
graduation recently).
1: Lutz PE, Pradhan AA, Goeldner C, Kieffer BL. Sequential and opposingalterations of
5-HT(1A) receptor function during withdrawal from chronic morphine. Eur
Neuropsychopharmacol. 2011 Nov;21(11):835-40.
2: Pradhan AA, Walwyn W, Nozaki C, Filliol D, Erbs E, Matifas A, Evans C,Kieffer BL.
Ligand-directed trafficking of the δ-opioid receptor in vivo: two paths toward
analgesic tolerance. J Neurosci. 2010 Dec 8;30(49):16459-68.
3: Pradhan AA, Yu XH, Laird JM. Modality of hyperalgesia tested, not type ofnerve
damage, predicts pharmacological sensitivity in rat models of neuropathic pain. Eur J
Pain. 2010 May;14(5):503-9.
4: Pradhan AA. Botulinum toxin: An emerging therapy in female bladder outlet
obstruction. Indian J Urol. 2009 Jul;25(3):318-20.
6: Pradhan AA, Gogate PR. Degradation of p-nitrophenol using acoustic cavitation and
Fenton chemistry. J Hazard Mater. 2010 Jan 15;173(1-3):517-22.
7: Pradhan AA, Becker JA, Scherrer G, Tryoen-Toth P, Filliol D, Matifas A, Massotte D,
Gavériaux-Ruff C, Kieffer BL. In vivo delta opioid receptor internalization controls
behavioral effects of agonists. PLoS One.2009;4(5):e5425.
8: Pradhan AA, Siau C, Constantin A, Clarke PB. Chronic morphine administration
results in tolerance to delta opioid receptor-mediated antinociception. Neuroscience.
2006 Aug 25;141(2):947-54.
9: Pradhan AA, Clarke PB. Pharmacologically selective block of mu
opioidantinociception by peptide nucleic acid antisense in absence of detectable
exvivo knockdown. Eur J Pharmacol. 2005 Jan 4;506(3):229-36.
10: Pradhan AA, Clarke PB. Comparison between delta-opioid receptor functional
response and autoradiographic labeling in rat brain and spinal cord. J CompNeurol.
2005 Jan 24;481(4):416-26. Pu
11: Pradhan AA, Levine MA. Warfarin use in atrial fibrillation: A random samplesurvey
of family physician beliefs and preferences. Can J Clin Pharmacol. 2002
Winter;9(4):199-202.
12: Pradhan AA, Cumming P, Clarke PB. [125I]Epibatidine-labelled nicotinicreceptors
in the extended striatum and cerebral cortex: lack of association with serotonergic
afferents. Brain Res. 2002 Nov 8;954(2):227-36. PubMed PMID:12414106.

19. Anna Taylor, PhD
PhD Canada
Canadian Citizen
Post-Doc UCLA
Assistant Professor
University of Alberta
Good Pedigree, most 1st authored
papers, impact was med-high,
NIDA relevance – pain (opioids) – 6
years out of post-doc.
Funded 2 years after review.
Weird things happen!
Cahill CM, Walwyn W, Taylor AMW, Pradhan AAA, Evans CJ. (2016). Allostatic mechanisms of opioid tolerance
beyond desensitization and downregulation. Trends Pharmacol Sci 37(11):963-976
Taylor AMW, Mehrabani S, Liu S, Taylor AJ, Cahill CM. (2016) Topography of microglial activation in sensory
and affect related brain regions in chronic pain. J Neurosci Res
Taylor AM, Becker S, Schweinhardt P, Cahill C. (2016) Mesolimbic dopamine signaling in acute and chronic
pain: implications for motivation, analgesia, and addiction. Pain 157(6):1194-8.
Taylor AMW, Castonguay A, Ghogha A, Vayssiere P, Pradhan AAA, Mehrabani S, Xue L, Wu J, Levitt P, De
Koninck Y, Evans CJ, Cahill CM. (2016) Neuroimmune regulation of GABAergic neurons within the ventral
tegmental area during withdrawal from chronic morphine. Neuropsychopharmacology, 41:949-959
Taylor AM, Castonguay A, Taylor, A, Murphy N, Ghogha A, Cook C, Xue L, Olmstead M, De Koninck Y, Evans C,
Cahill C (2015). Microglia disrupt mesolimbic reward circuitry in chronic pain. J Neurosci 35(22):8442-8450
Charrua A, Pinto R, Taylor A, Canelas A, Ribeiro-da-Silva A, Cruz CD, Birder LA, Cruz F (2015) Can the
adrenergic system be implicated in the pathophysiology of bladder pain syndrome/interstitial cystitis? A
clinical and experimental study. Neurourol Urodyn. Epub.
Cahill CM, Taylor AM, Cook C, Ong E, Moron JA, Evans CJ (2014). Does the kappa opioid receptor system
contribute to pain aversion? Front Pharmacol 15;5:253
Taylor AMW, Roberts KW, Pradhan AA, Walwyn W, Lutfy K, Carroll FI, Cahill CM, Evans CJ (2014). Kappa
opioid receptor-mediated analgesia is blocked by a delta opioid receptor agonist. British Journal of
Pharmacology, 172(2):e102334
Taylor AMW, Murphy NP, Evans CJ, Cahill CM (2014) Correlation between ventral striatal catecholamine
content and nociceptive thresholds in neuropathic mice. J Pain 15(8): 878-885.
Taylor, AMW. (2013) Pain and reward: How the affective-motivational system is perturbed in chronic pain.
Postdoctoral Research Journal. Vol 1, No.2.
Taylor, AMW and Ribeiro-da-Silva A. (2012). Consequences of the ablation of non-peptidergic afferents in an
animal model of trigeminal neuropathic pain. Pain. 153: 1311-1319.
Farmer, M.A., Taylor, AMW, Bailey, A.L., McIntyre, L.C., Milagrosa, Z.E., Crissman, H.P., Bennet, G.J., Ribeiro-
da-Silva, A., Binik, T.M., and Mogil, J.S. (2011) Recurrent vulvovaginal candidiasis as an etiology of provoked
vestibulodynia. Science Translational Medicine. 101ra91.
Cahill, C.M. and Taylor, AMW. (2011) A piece of the puzzle is revealed for delta opioid analgesia. Pain. 152
(6): 1217-1218.
Taylor, AMW. and Ribeiro-da-Silva, A. (2011). GDNF levels in the lower lip skin in rat model of trigeminal
neuropathic pain: Implications for non-peptidergic fiber re-innervation and parasympathetic sprouting. Pain.
52 (7): 1502-1510.
Taylor, AMW, Peleshok, J.C., and Ribeiro-da-Silva, A. (2009) Distribution of P2X3-immunoreactive fibers in
hairy and glabrous skin of the rat. J Comp Neurol. (514):555-566.
Riedl, M.S., Schnell, S.A., Overland, A.C., Chabot-Dore, A.J., Taylor, AMW, Ribeiro-da-Silva, A., Elde, R.P.,
Wilcox, G.L., and Stone, L.S. (2009) Coexpression of alpha2a adrenergic and delta opioid receptors in
substance P-Containing terminals in rat dorsal horn. J Comp Neurol. (513) 385-398.
Holdridge, S.C., Armstrong, S.A., Taylor, AMW, and Cahill, C.M. (2007) Behavioral and morphological evidence
for the involvement of glial cell activation of delta opioid receptor function: implications for the development
of opioid tolerance. Mol Pain. 3:7.